Stable insecticide compositions and methods for producing same

ABSTRACT

Insect controlling compositions including an N-substituted (6-haloalkylpyridin-3-yl)alkyl sulfoximine compound exhibiting increased stability, along with methods for preparing same, are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a Divisional of and claims priority to U.S.patent application Ser. No. 12/653,996 filed on Dec. 22, 2009, now U.S.Pat. No. 8,507,532, which claims priority to U.S. Provisional PatentApplication No. 61/203,600 filed on Dec. 26, 2008. The contents of theseapplications are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The invention disclosed in this document is related to the field ofpesticides and their use in controlling pests.

BACKGROUND OF THE INVENTION

Pests cause millions of human deaths around the world each year.Furthermore, there are more than ten thousand species of pests thatcause losses in agriculture. These agricultural losses amount tobillions of U.S. dollars each year. Termites cause damage to variousstructures such as homes. These termite damage losses amount to billionsof U.S. dollars each year. As a final note, many stored food pests eatand adulterate stored food. These stored food losses amount to billionsof U.S. dollars each year, but more importantly, deprive people ofneeded food.

Many pesticide compositions have been developed over time to destroypests and alleviate the damages they cause. With respect to at leastsome of these compositions, physical and chemical instabilities can leadto a reduction in pesticidal activity of the composition and/or presentcomplications when it comes time to apply the composition to a locuswhere pest control is necessary or desired. For example, physical andchemical instabilities can alter one or more properties of thecomposition which make it difficult or impossible to prepare appropriatesolutions of the composition for use. More particularly, many pesticidecompositions are provided in a concentrated formulation from themanufacturer and are subsequently diluted by an end user before theirapplication. During the time between manufacture and application, liquidforms of pesticide compositions can solidify as a result of chemical andphysical instabilities of the composition. Often times, thissolidification prevents or substantially impedes the dispersion of thecomposition into a solution suitable for application, resulting ingreater user burden and cost and/or wasted pesticide products. Moreover,when physical and chemical instabilities lead to a reduction inpesticidal activity of a composition, an increase in the concentrationat which the pesticide is applied and/or more frequent applications ofthe pesticide composition are often required. As a result, user costsand the cost to consumers can escalate. Therefore, a need exists for newpesticide compositions that exhibit increased chemical and physicalstability properties.

U.S. Patent Application Publication 2007/0203191 A1 describes certainN-substituted (6-haloalkylpyridin-3-yl)alkyl sulfoximine compounds andtheir use in controlling insects. It has now been discovered how toimprove the stability of compositions including one or more of thesecompounds over greater periods of time.

SUMMARY OF THE INVENTION

The present invention concerns novel compositions including anN-substituted (6-haloalkylpyridin-3-yl)alkyl sulfoximine compound andexhibiting increased stability, along with their use in controllinginsects and certain other invertebrates, particularly aphids and othersucking insects. This invention also includes new synthetic proceduresfor preparing the compositions and methods of controlling insects usingthe compositions.

This invention concerns compositions useful for the control of insects,especially useful for the control of aphids and other sucking insects,along with methods for preparing same. More specifically, in oneembodiment, a method includes providing a composition including a firstratio between stereoisomers of a compound having the formula (I)

wherein

X represents NO₂, CN or COOR⁴;

L represents a single bond or R¹, S and L taken together represent a 4-,5- or 6-membered ring;

R¹ represents (C₁-C₄)alkyl;

R² and R³ are distinct from each other and individually representhydrogen, methyl, ethyl, fluoro, chloro or bromo;

n is 1 when L represents a single bond and is 0 when R¹, S and L takentogether represents a 4-, 5- or 6-membered ring;

Y represents (C₁-C₄)haloalkyl, F, Cl, Br, or I; and

R⁴ represents (C₁-C₃)alkyl.

The method also includes heating the composition in a manner effectiveto provide a second, distinct ratio between the stereoisomers.

In one particular form of the method, the composition includes acompound of formula (I) wherein L represents a single bond, i.e., havingthe following structure wherein n is 1

wherein

X represents NO₂, CN or COOR⁴;

R¹ represents (C₁-C₄)alkyl;

R² and R³ are distinct from each other and individually representhydrogen, methyl, ethyl, fluoro, chloro or bromo;

Y represents (C₁-C₄)haloalkyl, F, Cl, Br, or I; and

R⁴ represents (C₁-C₃)alkyl.

In another particular form of the method, the composition includes acompound of formula (I) wherein R¹, S and L taken together form asaturated 5-membered ring, and n is 0, i.e., having the structure

wherein

X represents NO₂, CN or COOR⁴;

Y represents (C₁-C₄)haloalkyl, F, Cl, Br, or I; and

R⁴ represents (C₁-C₃)alkyl.

In yet other forms of the method, the composition includes compounds offormula (I) in one or more of the following classes:

(1) Compounds of formula (I) wherein X is NO₂ or CN, most preferably CN.

(2) Compounds of formula (I) wherein Y is CF₃.

(3) Compounds of formula (I) wherein R² and R³ are distinct from eachother and independently represent hydrogen, methyl or ethyl.

(4) Compounds of formula (I) wherein R¹ represents CH₃.

It will be appreciated by those skilled in the art that one or more ofthe compositions described herein may be comprised of combinations ofthe above described classes of the compound of formula (I).

In one form of the method, the heating is performed at a minimum ofabout 20° C. for at least about four hours. In another form, the heatingis performed at a minimum of about 50° C. from about four to aboutseventy two hours.

In another embodiment, a method includes providing a composition whichincludes a stereoisomeric mixture of a compound having the followingstructure:

wherein

X represents NO₂, CN or COOR⁴;

R¹ represents (C₁-C₄)alkyl;

R² and R³ are distinct from each other and individually representhydrogen, methyl, ethyl, fluoro, chloro or bromo;

Y represents (C₁-C₄)haloalkyl, F, Cl, Br, or I;

R⁴ represents (C₁-C₃)alkyl; and

the mixture is defined by a first pair of diastereomers and a secondpair of diastereomers.

The method also includes heating the composition to convert at least aportion of the second pair of diastereomers to the first pair ofdiastereomers.

In another embodiment, a composition includes a stereoisomeric mixtureof{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidedefined by a first pair of diastereomers and a second pair ofdiastereomers, wherein the first and second pairs of diastereomers arepresent at a ratio of at least about 3:1. In one form, the first andsecond pairs of diastereomers are present at a ratio from about 3:1 to100:1. In another form, the first and second pairs of diastereomers arepresent at a ratio from about 3:1 to 40:1.

In yet another embodiment, a method includes applying to a locus wherecontrol is desired an insect-inactivating amount of a pesticidecomposition.

Still, further embodiments, forms, features, aspects, benefits, objects,and advantages of the present invention shall become apparent from thedetailed description and examples provided.

Substituents Non-Exhaustive List

The examples given for the substituents are (except for halo)non-exhaustive and must not be construed as limiting the inventiondisclosed in this document.

“alkyl” (including derivative terms such as alkoxy) means straightchain, branched chain and cyclic groups including, for example, methyl,ethyl, 1-methylethyl, propyl, 1,1-dimethylethyl and cyclopropyl.

“alkoxy” means an alkyl further consisting of a carbon-oxygen singlebond, for example, methoxy, ethoxy, propoxy, isopropoxy, 1-butoxy,2-butoxy, isobutoxy, tert-butoxy, pentoxy, 2-methylbutoxy,1,1-dimethylpropoxy, hexoxy, heptoxy, octoxy, nonoxy, and decoxy.

“aryl” means a cyclic, aromatic substituent consisting of hydrogen andcarbon, for example, phenyl, naphthyl, and biphenylyl.

“halo” means fluoro, chloro, bromo, and iodo.

“haloalkyl” means an alkyl group substituted with from one to themaximum possible number of halogen atoms, all combinations of halogensincluded.

DETAILED DESCRIPTION OF THE INVENTION

Throughout this document, all temperatures are given in degrees Celsius,and all percentages are weight percentages unless otherwise stated.

The compounds of formula (Ia), wherein R¹, R², R³, R⁴, X, and Y are aspreviously defined, L is a single bond and n is 1, can be prepared bythe methods illustrated in Scheme A:

In step a of Scheme A, sulfide of formula (A) is oxidized withmeta-chloroperoxybenzoic acid (mCPBA) in a polar solvent below 0° C. toprovide sulfoxide of formula (B). In most cases, dichloromethane is thepreferred solvent for oxidation.

In step b of Scheme A, sulfoxide (B) is iminated with sodium azide inthe presence of concentrated sulfuric acid in an aprotic solvent underheating to provide sulfoximine of formula (C). In most cases, chloroformis the preferred solvent for this reaction.

In step c of Scheme A, the nitrogen of sulfoximine (C) can be eithercyanated with cyanogen bromide in the presence of a base, or nitratedwith nitric acid in the presence of acetic anhydride under mildlyelevated temperature, or carboxylated with alkyl (R4) chloroformate inthe presence of base such as 4-dimethylaminopyridine (DMAP) to provideN-substitutedsulfoximine (Ia). Base is required for efficient cyanationand carboxylation and the preferred base is DMAP, whereas sulfuric acidis used as catalyst for efficient nitration reaction.

The compounds of formula (Ia), wherein X represents CN and R¹, R², R³,R⁴ and Y are as previously defined and n is 1, can be prepared by themild and efficient method illustrated in Scheme B.

In step a of Scheme B, sulfide is oxidized with iodobenzene diacetate inthe presence of cyanamide at 0° C. to give sulfilimine (D). The reactioncan be carried out in a polar aprotic solvent like CH₂Cl₂.

In step b of Scheme B, the sulfilimine (D) is oxidized with mCPBA. Abase such as potassium carbonate is employed to neutralize the acidityof mCPBA. Protic polar solvents such as ethanol and water are used toincrease the solubility of the sulfilimine starting material and thebase employed. The sulfilimine (D) can also be oxidized with aqueoussodium or potassium periodinate solution in the presence of catalystruthenium trichloride hydrate or similar catalyst. The organic solventfor this catalysis can be polar aprotic solvent such as CH₂Cl₂,chloroform, or acetonitrile.

The α-carbon of the N-substituted sulfoximine of formula (Ia), i.e.,n=1, R³=H in the (CR²R³) group adjacent to the N-substituted sulfoximinefunction can be further alkylated or halogenated (R⁵) in the presence ofa base such as potassium hexamethyldisilamide (KHMDS) to giveN-substituted sulfoximines of formula (Ib), wherein R¹, R², R³, R⁴, X, Land Y are as previously defined and Z is an appropriate leaving group,as illustrated in Scheme C. The preferred leaving groups are iodide(R⁵=alkyl), benzenesulfonimide (R⁵=F), tetrachloroethene (R⁵=Cl), andtetrafluoroethene (R⁵=Br).

The starting sulfides (A) in Scheme A can be prepared in different waysas illustrated in Schemes D, E, F, G and H.

In Scheme D, the sulfide of formula (A₁), wherein R¹, R² and Y are aspreviously defined, n=1, and R³=H, can be prepared from the chloride offormula (D) by nucleophilic substitution with the sodium salt of analkyl thiol.

In Scheme E, the sulfide of formula (A₄), wherein R¹, S and L takentogether represents a 4-, 5- or 6-membered ring (m=0, 1, or 2) and n is0 can be prepared from the corresponding substitutedchloromethylpyridine by treatment with thiourea, hydrolysis andsubsequent alkylation with the appropriate bromo chloroalkane (m=0, 1,or 2) under aqueous base conditions, and cyclization in the presence ofa base like potassium-t-butoxide in a polar aprotic solvent such as THF.

Sulfides of formula (A₁), wherein R¹, R²=CH₃, Y as previously defined,and R³=H, can be prepared alternatively via methods illustrated inScheme F. Accordingly, the appropriate enone is coupled withdimethyl-aminoacrylonitrile and cyclized with ammonium acetate in DMF toyield the corresponding 6-substituted nicotinonitrile. Treatment withmethylmagnesium bromide, reduction with sodium borohydride, chlorinationwith thionyl chloride, and nucleophilic substitution with the sodiumsalt of an alkyl thiol provide desired sulfides (A₁).

Sulfides of formula (A₁), wherein R¹=methyl or ethyl, R² and R³ aredistinct from each other and independently represent hydrogen, methyl orethyl, and Y is as previously defined can be prepared via a variation ofScheme F, depicted in Scheme G, wherein enamines, formed from theaddition of an amine, e.g., pyrrolidine, with the Michael adduct ofcertain sulfides with appropriately substituted α,β-unsaturatedaldehydes, are coupled with substituted enones and cyclized withammonium acetate in acetonitrile to yield the desired sulfides (A₁).

In Scheme H, sulfides of formula (A₁), wherein Y is a fluoroalkyl group,R¹, R² and R³ are as previously defined, and n=1 can be prepared fromthe 6-acylpyridine or 6-formyl pyridine by reaction withdiethylaminosulfur trifluoride (DAST). Subsequent halogenation of the3-methyl group with NBS followed by nucleophilic substitution with thesodium salt of an alkyl thiol furnishes the desired sulfide.

Examples of nonlimiting compounds according to formula (I):

Example I Preparation of[1-(6-trifluoromethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(2)

To a solution of 3-chloromethyl-6-(trifluoromethyl)pyridine (5.1 g, 26mmol) in dimethyl sulfoxide (DMSO; 20 mL) was added in one portionsodium thiomethoxide (1.8 g, 26 mmol). A violent exothermic reaction wasobserved which resulted in the reaction turning dark. The reaction wasstirred for 1 hr, then additional sodium thiomethoxide (0.91 g, 13 mmol)was added slowly. The reaction was stirred overnight, after which it waspoured into H₂O and several drops of conc. HCl were added. The mixturewas extracted with Et₂O (3×50 mL) and the organic layers combined,washed with brine, dried over MgSO₄ and concentrated. The crude productwas purified by chromatography (Prep 500, 10% acetone/hexanes) tofurnish the sulfide (A) as a pale yellow oil (3.6 g, 67%). ¹H NMR (300MHz, CDCl₃) δ 8.6 (s, 1H), 7.9 (d, 1H), 7.7 (d, 1H), 3.7 (s, 2H), 2.0(s, 3H); GC-MS: mass calcd for C₈H₈F₃NS [M]⁺ 207. Found 207.

To a solution of sulfide (A) (3.5 g, 17 mmol) and cyanamide (1.4 mg, 34mmol) in CH₂Cl₂ (30 mL) at 0° C. was added iodobenzenediacetate (11.0 g,34 mmol) all at once. The reaction was stirred for 30 min, then allowedto warm to room temperature overnight. The mixture was diluted withCH₂Cl₂ (50 mL) and washed with H₂O. The aqueous layer was extracted withethyl acetate (4×50 mL), and the combined CH₂Cl₂ and ethyl acetatelayers dried over MgSO₄ and concentrated. The crude product wastriturated with hexanes and purified by chromatography (chromatotron, 60percent acetone/hexanes) to furnish the sulfilimine (B) as a yellow gum(0.60 g, 14 percent). IR (film) 3008, 2924, 2143, 1693 cm⁻¹; ¹H NMR (300MHz, CDCl₃) δ 8.8 (s, 1H), 8.0 (d, 1H), 7.8 (d, 1H), 4.5 (d, 1H), 4.3(d, 1H), 2.9 (s, 3H); LC-MS (ESI): mass calcd for C₉H₉F₃N₃S [M+H]⁺248.04. Found 248.

To a solution of m-chloroperbenzoic acid (mCPBA; 80 percent, 1.0 g, 4.9mmol) in EtOH (10 mL) at 0° was added a solution of K₂CO₃ (1.4 g, 10mmol) in H₂O (7 mL). The solution was stirred for 20 min, then asolution of sulfilimine (B) (0.60 g, 2.4 mmol) in EtOH (20 mL) was addedall at once. The reaction was stirred at 0° C. for 30 min, then allowedto warm to room temperature over the course of 1 hr. The reaction wasthen quenched with aq. sodium bisulfite and the mixture was concentratedto remove ethanol. The resulting mixture was extracted with CH₂Cl₂ andthe combined organic layers dried over MgSO₄ and concentrated. The crudeproduct was purified by chromatography (chromatotron, 50 percentacetone/hexanes) to furnish the sulfoximine (1) as an off-white solid(0.28 g, 44 percent). Mp=135-137° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.8 (s,1H), 8.1 (d, 1H), 7.8 (d, 1H), 4.7 (m, 2H), 3.2 (s, 3H); LC-MS (ELSD):mass calcd for C₉H₉F₃N₃₀S [M+H]⁺ 264.04. Found 263.92.

To a solution of sulfoximine (1) (50 mg, 0.19 mmol) andhexamethylphosphoramide (HMPA; 17 μL, 0.10 mmol) in tetrahydrofuran(THF; 2 mL) at −78° C. was added potassium hexamethyldisilazane (KHMDS;0.5 M in toluene, 420 μL, 0.21 mmol) dropwise. The solution was stirredat −78° C. for an additional 20 min, after which iodomethane (13 μL,0.21 mmol) was added. The reaction was allowed to warm to roomtemperature over the course of 1 hr, after which it was quenched withsatd. aq. NH₄Cl and extracted with CH₂Cl₂. The organic layer was driedover Na₂SO₄, concentrated, and the crude product purified bychromatography (chromatotron, 70 percent acetone/CH₂Cl₂) to furnish thesulfoximine (2) as a 2:1 mixture of diastereomers (colorless oil; 31 mg,59 percent). Sulfoximine (2) is commonly known as sulfoxaflor, furtherdetails of which are available athttp://www.alanwood.net/pesticides/index_cn_frame.html. According to arevised version of IUPAC nomenclature, sulfoximine (2) is also referredto as[methyl(oxido){1-[6-(trifluoromethyl)-3-pyridyl]ethyl}-λ⁶-sulfanylidene]cyanamide,and the CAS name given to sulfoximine (2) isN-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinil]ethyl]-λ⁴-sulfanylidene]cyanamide.¹H NMR (300 MHz, CDCl₃) S (major diastereomer) 8.8 (s, 1H), 8.1 (d, 1H),7.8 (d, 1H), 4.6 (q, 1H), 3.0 (s, 3H), 2.0 (d, 3H); (minor diastereomer)8.8 (s, 1H), 8.1 (d, 1H), 7.8 (d, 1H), 4.6 (q, 1H), 3.1 (s, 3H), 2.0 (d,3H); LC-MS (ELSD): mass calcd for C₁₀H₁₀F₃N₃OS [M+H]⁺ 278.06. Found278.05.

Example II Preparation of2-(6-trifluoromethylpyridin-3-yl)-1-oxido-tetrahydro-1H-1λ⁴-thien-1-ylidenecyanamide(3)

To a suspension of thiourea (1.2 g, 16 mmol) in EtOH (25 mL) was added asolution of 3-chloromethyl-6-(trifluoromethyl)pyridine in EtOH (10 mL).The suspension was stirred at room temperature for 2 days, during whicha white precipitate formed. The precipitate was filtered to give thedesired amidine hydrochloride as a white solid (2.4 g, 58 percent).Mp=186-188° C. No further attempt was made to purify the product. ¹H NMR(300 MHz, CDCl₃) δ 8.9 (bs, 4H), 8.4 (s, 1H), 7.6 (d, 1H), 7.3 (d, 1H),4.2 (s, 2H); LC-MS (ELSD): mass calcd for C₈H₈FN₃S [M+H]⁺ 236.05. Found236.01.

To a solution of amidine hydrochloride (A) (1.8 g, 6.8 mmol) in H₂O (12mL) at 10° C. was added 10 N NaOH (0.68 mL, 6.8 mmol), which resulted inthe formation of a white precipitate. The suspension was heated at 100°C. for 30 min, then cooled back down to 10° C. Additional 10 N NaOH(0.68 mL, 6.8 mmol) was then added, followed by 1-bromo-3-chloropropane(0.67 mL, 6.8 mmol) all at once. The reaction was stirred at roomtemperature overnight, then extracted with CH₂Cl₂. The combined organiclayers were washed with brine, dried over Na₂SO₄ and concentrated tofurnish the sulfide (B) as a colorless oil (1.7 g, 96 percent). Nofurther attempt was made to purify the product. ¹H NMR (300 MHz, CDCl₃)δ 8.6 (s, 1H), 7.8 (d, 1H), 7.6 (d, 1H), 3.8 (s, 2H), 3.6 (t, 2H), 2.6(t, 2H), 2.0 (quint, 2H).

To a suspension of potassium tert-butoxide (1.5 g, 13 mmol) in THF (12mL) was added HMPA (1.7 mL, 10 mmol) followed by a solution of sulfide(B) (1.8 g, 6.7 mmol) in THF (3 mL) dropwise. The reaction was allowedto stir at room temperature overnight, followed by concentration andpurification by chromatography (Biotage, 40 percent EtOAc/hexanes) tofurnish cyclized product (C) as an orange oil (230 mg, 15 percent). ¹HNMR (300 MHz, CDCl₃) δ 8.7 (s, 1H), 8.0 (d, 1H), 7.6 (d, 1H), 4.6 (dd,1H), 3.2 (m, 1H), 3.1 (m, 1H), 2.5 (m, 1H), 2.3 (m, 1H), 2.1-1.9 (m,2H).

To a solution of sulfide (C) (230 mg, 0.99 mmol) and cyanamide (83 mg,2.0 mmol) in CH₂Cl₂ (5 mL) at 0° C. was added iodobenzenediacetate (350mg, 1.1 mmol) all at once. The reaction was stirred for 3 hr, thenconcentrated and the crude product purified by chromatography(chromatotron, 50 percent acetone/hexanes) to furnish the sulfilimine(D) as an orange oil (150 mg, mixture of diastereomers, 56 percent). ¹HNMR (300 MHz, CDCl₃) 8.8 (s, 1H), 7.9 (d, 1H), 7.8 (d, 1H), 4.8 (dd,1H), 3.5 (m, 2H), 2.9-2.7 (m, 2H), 2.6 (m, 1H), 2.3 (m, 1H).

To a solution of mCPBA (80 percent, 180 mg, 0.82 mmol) in EtOH (3 mL) at0° C. was added a solution of K₂CO₃ (230 mg, 1.7 mmol) in 1-120 (1.5mL). The solution was stirred for 20 min, then a solution of sulfilimine(D) (150 mg, 0.55 mmol) in EtOH (2 mL) was added all at once. Thereaction was stirred at 0° C. for 45 min, after which the solvent wasdecanted into a separate flask and concentrated to give a white solid.The solid was slurried in CHCl₃, filtered, and concentrated to furnishpure sulfoximine (3) as a colorless oil (72 mg, 44 percent). ¹H NMR (300MHz, CDCl₃) 8 (1.5:1 mixture of diastereomers) 8.8 (s, 2H), 8.0 (d, 2H),7.8 (d, 2H), 4.7 (q, 1H), 4.6 (q, 1H), 4.0-3.4 (m, s, 4H), 3.0-2.4 (m,8H); LC-MS (ELSD): mass calcd for C₁₁H₁₁F₃N₃OS [M+H]⁺ 290.06. Found289.99.

Example III Preparation of(1-{6-[chloro(difluoro)methyl]pyridin-3-yl}ethyl)(methyl)-oxido-λ⁴-sulfanylidenecyanamide(4)

(3E)-1-Chloro-4-ethoxy-1,1-difluorobut-3-en-2-one (7.36 g, 40 mmol) wasdissolved in dry toluene (40 mL) and treated with3-dimethylaminoacrylonitrile (4.61 g, 48 mmol) at room temperature. Thesolution was heated at 100° C. for 3.5 hr. The solvent was then removedunder reduced pressure and the remaining mixture was re-dissolved in DMF(20 mL), treated with ammonium acetate (4.62 g, 60 mmol) and stirred atroom temperature overnight. Water was added to the reaction mixture andthe resulting mixture was extracted with ether-CH₂CH₂ (1:2, v/v) twice.The combined organic layer was washed with brine, dried, filtered andconcentrated. The residue was purified on silica gel to give 3.1 g of6-[chloro(difluoro)methyl]nicotinonitrile (A) as light colored oil in 41percent yield. GC-MS: mass calcd for C₇H₃ClF₂N₂ [M]⁺ 188. Found 188.

6-[chloro(difluoro)methyl]nicotinonitrile (A) (3.0 g 15.8 mmol) wasdissolved in anhydrous ether (25 mL) and cooled in an ice-water bath. Asolution of 3 M of methylmagnesium bromide in hexane (6.4 mL, 19 mmol)was added through a syringe. After the addition was over, the mixturewas stirred at 0° C. for 5 hr and then at room temperature for 10 hr.The reaction was quenched slowly with 1 N citric acid aqueous solutionat 0° C. and the resulting mixture was stirred at room temperature for 1hr. The pH was adjusted back to pH 7 with saturated NaHCO₃ aqueoussolution. The two phases were separated and the aqueous phase wasextracted with ethyl acetate twice. The combined organic layer waswashed with brine, dried over anhydrous Na₂SO₄, filtered, andconcentrated. The remaining mixture was purified on silica gel elutedwith 15 percent acetone in hexane to give 0.88 g of the desired product1-{6-[chloro(difluoro)methyl]pyridin-3-yl}-ethanone (B) as brownish oilin 30 percent yield. GC-MS: mass calcd for C₈H₆ClF₂NO [M]⁺ 205. Found205.

To a solution of 1-{6-[chloro(difluoro)methyl]pyridin-3-yl}ethanone (B)(0.85 g, 4.14 mmol) in MeOH (10 mL) at 0° C. was added NaBH₄ (0.16 g,4.14 mmol). The mixture was stirred for 30 min and 2 M HCl aqueoussolution was added until pH reached 7. Solvent was removed under reducedpressure and the remaining mixture was extracted with CH₂Cl₂ (2×50 mL).The combined organic layer was dried over anhydrous Na₂SO₄, filtered,concentrated, and dried in vacuo to give 0.798 g of analytically pure1-{6-[chloro(difluoro)methyl]-pyridin-3-yl}ethanol (C) on GC-MS as alight yellow oil in 93 percent yield. GC-MS: mass calcd for C₅H₆ClF₂NO[M]⁺ 207. Found 207.

To a solution of 1-{6-[chloro(difluoro)methyl]-pyridin-3-yl}ethanol(0.78 g, 3.77 mmol) in CH₂Cl₂ (40 mL) was added thionyl chloride (0.54mL, 7.54 mmol) dropwise at room temperature. After 1 hr, the reactionwas quenched slowly with saturated NaHCO₃ aqueous solution and the twophases were separated. The organic layer was dried over Na₂SO₄,filtered, concentrated, and dried in vacuum to give 0.83 g of the crude2-[chloro(difluoro)methyl]-5-(1-chloroethyl)pyridine (D) as brown oil in98 percent yield, which was directly used for the next step reaction.GC-MS: mass calcd for C₈H₇Cl₂F₂N [M]⁺ 225. Found 225.

To a solution of 2-[chloro(difluoro)methyl]-5-(1-chloroethyl)pyridine(D) (0.81 g, 3.6 mmol) in ethanol (10 mL) was added sodium thiomethoxide(0.52 g, 7.4 mmol) under stirring in one portion at 0° C. After 10 min,the mixture was allowed to warm to room temperature and stirredovernight. The solvent ethanol was then removed under reduced pressureand the residue was re-taken into ether/CH₂Cl₂ and brine. The two phaseswere separated and the organic layer was extracted with CH₂Cl₂ one moretime. The combined organic layer was dried over anhydrous Na₂SO₄,filtered, concentrated, purified on silica gel using 5 percent ethylacetate in hexane to give 0.348 g of the2-[chloro(difluoro)methyl]-5-[1-(methylthio)ethyl]pyridine (E) in 40percent yield GC-MS: mass calcd for C₉H₁₀ClF₂NS [M]⁺ 237. Found 237.

To a stirred solution of2-[chloro(difluoro)methyl]-5-[1-(methylthio)-ethyl]pyridine (E) (0.32 g,1.35 mmol) and cyanamide (0.058 g, 1.35 mmol) in THF (7 mL) was addediodobenzene diacetate (0.44 g, 1.35 mmol) in one portion at 0° C. andthe resulting mixture was stirred at this temperature for 1 hr and thenat room temperature for 2 hr. The solvent was then removed under reducedpressure and the resulting mixture was dissolved in CH₂Cl₂, washed withhalf-saturated brine, dried over anhydrous Na₂SO₄, filtered,concentrated, and purified on silica gel using 50 percent acetone inhexane to give 0.175 g of(1-{6-[chloro-(difluoro)methyl]pyridin-3-yl}ethyl)(methyl)-λ⁴-sulfanylidenecyanamide(F) as light-yellow oil in 48 percent yield. ¹H NMR (300 MHz, CDCl₃) δ8.71 (d, J=1.8 Hz, 1H), 7.91 (dd, J=8.4, 1.8 Hz, 1H) 7.78 (d, J=8.4 Hz,1H), 4.42 (q, J=6.9 Hz, 1H), 2.64 (s, 3H), 1.92 (d, J=6.9 Hz, 3H);LC-MS: mass calcd for C₁₀H₁₀ClF₂N₃S [M+1]⁺ 278. Found 278.

To a stirred solution of(1-{6-[chloro(difluoro)methyl]pyridin-3-yl}ethyl)-(methyl)-λ⁴-sulfanylidenecyanamide(F) (0.16 g, 0.6 mmol) in ethanol (10 mL) was added 20 percent potassiumcarbonate aqueous solution (1.24 g, 1.8 mmol) at 0° C. under stirring.After 10 min stirring, 80 percent mCPBA (0.19 g, ca 0.9 mmol) was addedto the mixture, which was stirred at 0° C. for 2 hr after which thereaction was quenched with a spatula of solid sodium thiosulfate. Mostof the solvent ethanol was removed under reduced pressure and an aqueoussaturated NaHCO₃-brine (1:1, v/v) solution was added and the mixtureextracted with chloroform three times. The combined organic layer wasdried over Na₂SO₄, filtered and concentrated. The residue was purifiedon silica gel using 35-50 percent acetone in hexane as eluent to give0.092 g of the product(1-{6-[chloro(difluoro)-methyl]pyridin-3-yl}ethyl)(methyl)oxido-λ⁴-sulfanylidenecyanamide(4) as colorless oil in 57 percent yield. ¹H NMR (300 MHz, CDCl₃) δ 8.79(s, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 4.73 (q, J=7.2Hz, 1H), 3.16 and 3.11 (2 s, 3H, a mixture of two diastereomeric α-CH3groups between the sulfoximine and the pyridine tail), 2.00 (d, J=7.2Hz, 3H); LC-MS: mass calcd for C₁₀H₁₀ClF₂N₃OS [M−1]⁺ 292. Found 292.

Example IV Preparation of[1-(6-trichloromethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(5)

A mixture of 5-ethylpyridine-2-carboxylic acid (1.98 g, 13 mmol),phenyl-phosphonic dichloride (2.8 g, 14.3 mmol), phosphoruspentachloride (7.7 g, 32 mmol) was stirred and slowly heated. Once aclear yellow liquid was formed, the mixture was heated to refluxovernight. After cooling, the volatiles were removed under reducedpressure. The residue was carefully poured into saturated sodiumcarbonate aqueous solution cooled in an ice-water bath. The aqueousphase was then extracted with CH₂Cl₂ two times. The combined organiclayer was washed with brine, dried over anhydrous Na₂SO₄, filtered,concentrated, and partially purified on silica gel eluted with 10percent EtOAc in hexane to give 2.7 g of crude product containing both5-ethyl-2-(trichloromethyl)pyridine and5-(1-chloro-ethyl)-2-(trichloromethyl)pyridine in an approximate 3:1ratio (GC data, masses calcd for C₈H₈Cl₃N and C₈H₇Cl₄N [M]⁺ 223 and 257respectively. Found 223 and 257 respectively).

A mixture of the above-mentioned crude product (2.6 g) in carbontetrachloride (100 mL) was then treated with 80 percent ofN-bromosuccinimide (1.9 g, 11 mmol) and benzoylperoxide (0.66 g, 0.275mmol) and then refluxed overnight. The solid was filtered off, thefiltrate concentrated and the resulting residue purified on silica gelusing 4 percent EtOAc in hexane to give 1.0 g of the desired product5-(1-bromoethyl)-2-(trichloromethyl)pyridine (A) as a yellow solid. Thecombined yield for the two steps was 25 percent. GC-MS: mass calcd forC₈H₇BrCl₃N [M−I−Cl]⁺ 266. Found 266.

A solution of 5-(1-bromoethyl)-2-(trichloromethyl)pyridine (A) (0.95 g,3.14 mmol) in ethanol (15 mL) was treated with sodium thiomethoxide(0.44 g, 6.29 mmol) portionwise at 0° C. The mixture was stirred at roomtemperature overnight. The solvent ethanol was then removed under areduced pressure and the residue was re-taken into CH₂Cl₂ and brine. Thetwo phases were separated and the organic layer was dried over anhydrousNa₂SO₄, filtered, concentrated. The residue was purified on silica gelusing 5 percent EtOAc in hexane to give 0.57 g of the partially pure5-[1-(methylthio)ethyl]-2-(trichloromethyl)pyridine (B) in 67 percentcrude yield. GC-MS: mass calcd for C₉H₁₀Cl₃NS [M]⁺ 269. Found 269.

To a stirred solution of5-[1-(methylthio)ethyl]-2-(trichloromethyl)-pyridine (B) (0.55 g 2.3mmol) and cyanamide (0.097 g, 2.3 mmol) in THF (7 mL) cooled to 0° C.was added iodobenzene diacetate (0.75 g, 2.3 mmol) in one portion. Theresulting mixture was stirred at 0° C. for 1 hr and then at roomtemperature for 2 hr. The solvent was removed in vacuo and the resultingmixture was purified on silica gel using 50 percent acetone in hexane togive 0.254 g of(1E)-methyl{1-[6-(trichloromethyl)pyridin-3-yl]ethyl}-sulfanylidenecyanamide(C) as an off-white solid in 40 percent yield. ¹H NMR for thediastereomeric mixture (300 MHz, ds-acetone) δ 8.87 (s, 1H), 8.21-8.25(m, 2H), 4.65-4.76 (m, 1H), 2.86-2.66 (m, 3H), 1.88-1.92 (m, 3H).

To a stirred solution of(1E)-methyl{1-[6-(trichloromethyl)pyridin-3-yl]ethyl}-λ⁴-sulfanylidenecyanamide(C) (0.20 g, 0.65 mmol) in ethanol (15 mL) was added 20 percent aqueouspotassium carbonate solution (1.3 mL) at 0° C., followed by addition of80 percent mCPBA. The resulting mixture was stirred for 2 hr at 0° C.and then quenched with solid sodium thiosulfate. Most of the solvent wasevaporated and 1:1 aqueous saturated NaHCO₃-brine (v/v) was added andthe mixture was extracted with chloroform three times. The combinedorganic layer was dried over anhydrous Na₂SO₄, filtered andconcentrated. The residue was purified on silica gel using 40 percentacetone in hexane to give 0.10 g of[1-(6-trichloromethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidene-cyanamide(5) as colorless oil in 50 percent yield. ¹H NMR (300 MHz, CDCl₃) δ 8.83(s, 1H), 8.12-8.23 (m, 1H), 5.15 (q, 1H), 3.37 and 3.28 (2 s, 3H, amixture of two diastereomeric α-CH₃ groups between the sulfoximine andthe pyridine tail), 2.03 (d, 3H); LC-MS: mass calcd for C₁₀H₁₂Cl₃N₃₀S[M+1]⁺ 328. Found 328.

Example V Preparation of[1-(6-difluoromethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(6)

To a solution of 2-iodo-5-bromopyridine (18.4 g, 65 mmol) in THF (100mL) at −15° C. was added isopropylmagnesium chloride (2M, 35 mL, 70mmol) dropwise at a rate such that the temperature of the reaction didnot exceed 0° C. The reaction was stirred at −15° C. for 1 h, then DMF(7.5 mL, 97 mmol) was added dropwise at a rate such that the temperatureof the reaction did not exceed 0° C. The reaction was stirred for 30min, then warmed to room temperature for an additional 1 h. The reactionwas cooled back down to 0° C. and 2 N HO (80 mL) was added dropwise,maintaining the temperature below 20° C. After stirring for 30 min, 2 NNaOH was added until pH 7 was reached. The organic layer was thenseparated and the aqueous layer extracted with CH₂Cl₂ (3×). The combinedorganic layers were dried over MgSO₄, concentrated and purified by flashchromatography (SiO₂, 10% EtOAc/hexanes) to furnish5-bromopyridine-2-carbaldehyde (A) as a white solid (7.3 g, 60 percent).¹H NMR (300 MHz, CDCl₃) δ 10.0 (s, 1H), 8.9 (s, 1H), 8.0 (d, 1H), 7.8(d, 1H).

To a cooled solution of 5-bromopyridine-2-carbaldehyde (A) (7.0 g, 38mmol) in CH₂Cl₂ (300 mL) at −78° C. was added diethylaminosulfurtrifluoride (DAST, 10.8 mL, 83 mmol). The reaction was allowed to warmto room temperature over the course of 6 h, then it was quenched slowlywith H₂O, washed with saturated aqueous NaHCO₃ and dried over Na₂SO₄.Concentration and purification by silica gel plug (CH₂Cl₂ eluent)furnished 5-bromo-2-difluoromethylpyridine (B) as brown crystals (5.3 g,67 percent). ¹H NMR (300 MHz, CDCl₃) δ 8.8 (s, 1H), 8.0 (d, 1H), 7.6 (d,1H), 6.6 (t, 1H).

To a solution of 5-bromo-2-difluoromethylpyridine (B) (1.8 g, 8.6 mmol)in THF (40 mL) at 25° C. was added isopropylmagnesium chloride (2M, 8.6mL, 17 mmol) dropwise. The reaction was allowed to stir for 2 h, thenDMF (660 μL, 8.6 mmol) was added and the reaction was stirred for anadditional 22 h. The reaction was quenched with 2M HCl and basified with1M NaOH until pH 7 reached. The organic layer was separated and theaqueous layer was extracted with CH₂Cl₂. The combined organic layerswere dried over Na₂SO₄, concentrated and purified by flashchromatography (10 percent EtOAc/hexanes) to furnish6-difluoromethylpyridine-3-carbaldehyde (C) as an orange oil (320 mg, 24percent).

To a solution of 6-difluoromethylpyridine-3-carbaldehyde (C) (500 mg,3.2 mmol) in MeOH (10 mL) at 0° C. was added NaBH₄ (60 mg, 1.6 mmol).The reaction was allowed to stir for 30 min, then 2M HCl was added untilpH 2 was reached. The resulting solution was extracted with CH₂Cl₂ (3×)and the combined organic layers dried over Na₂SO₄ and concentrated tofurnish (6-difluoromethyl-pyridin-3-yl)methanol (D) as an orange oil(420 mg, 82 percent) which was used in the next step without furtherpurification. ¹H NMR (300 MHz, CDCl₃) δ 8.6 (s, 1H), 7.9 (d, 1H), 7.6(d, 1H), 6.6 (t, 1H), 4.8 (s, 2H).

To a solution of (6-difluoromethylpyridin-3-yl)methanol (D) (450 mg, 2.8mmol) in CH₂Cl₂ (10 mL) at room temperature was SO₂Cl (230 μL, 3.1mmol). The reaction was allowed to stir for 1 h, then the reaction wasquenched slowly with saturated aqueous NaHCO₃. The aqueous phase wasextracted with CH₂Cl₂ (3×) and the combined organic layers were driedover Na₂SO₄ and concentrated. The resulting solution was extracted withCH₂Cl₂ (3×) and the combined organic layers dried over Na₂SO₄ andconcentrated to furnish 5-chloromethyl-2-difluoromethylpyridine (E) as areddish brown oil (490 mg, 98%) which was used in the next step withoutfurther purification. ¹H NMR (300 MHz, CDCl₃) δ 8.7 (s, 1H), 7.9 (d,1H), 7.6 (d, 1H), 6.6 (t, 1H), 4.6 (s, 2H).

To a solution of sodium thiomethoxide (240 mg, 3.3 mmol) in EtOH (10 ml)at room temperature was added a solution of5-chloromethyl-2-difluoromethylpyridine (E) (490 mg, 2.8 mmol) in EtOH(3 mL). The reaction was allowed to stir for 9 h, then the reaction wasconcentrated, taken up in Et₂O, and washed with H₂O. The organic phasewas dried over Na₂SO₄ and concentrated to furnish2-difluoromethyl-5-methylthiomethyl-pyridine (F) as an orange oil (422mg, 81%) which was used in the next step without further purification.¹H NMR (300 MHz, CDCl₃) δ 8.6 (s, 1H), 7.8 (d, 1H), 7.6 (d, 1H), 6.6 (t,1H), 3.7 (s, 2H), 2.0 (s, 3H).

[(6-Difluoromethylpyridin-3-yl)methyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(G) was synthesized from 2-difluoromethyl-5-methylthiomethylpyridine (F)in two steps as described in Examples I-B and I-C. Isolated as a whitesolid (51% yield). ¹H NMR (300 MHz, CDCl₃) δ 8.7 (s, 1H), 8.0 (d, 1H),7.8 (d, 1H), 6.7 (t, 1H), 4.7 (dd, 2H), 3.2 (s, 3H); LC-MS (ELSD): masscalcd for C₉H₁₀F₂N₃OS [M+H]⁺, 246. Found 246.

[1-(6-difluoromethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(6) was synthesized from[(6-difluoromethylpyridin-3-yl)methyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(G) in one step as described in Example I. Isolated as a colorless oil(74 percent yield) and a 1:1 mixture of diastereomers. ¹H NMR (300 MHz,CDCl₃) δ (mixture of two diastereomers) 8.7 (s, 2H), 8.0 (d, 2H), 7.8(d, 2H), 6.7 (t, 2H), 4.6 (q, 2H), 3.1 (s, 3H), 3.0 (s, 3H), 2.0 (d,6H), LC-MS (ELSD): mass calcd for C₁₀H₁₂F₂N₃OS [M+H]⁺, 260. Found 260.

Example VI Preparation of[1-(6-pentafluoroethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(7)

(E)-1-Ethoxy-4,4,5,5,5-pentafluoropent-1-en-3-one (1.09 g, 5 mmol) inanhydrous ethyl ether (5 mL) was treated with1-((E)-3-methylthiobut-1-enyl)pyrrolidine (0.85 g, 5 mmol) in 2 mL dryether at −15° C. over a period of 5 min and the reaction was continuedfor 20 min. Then the temperature was allowed to rise to room temperatureand the reaction continued for 3 h. The solvent was removed underreduced pressure and the residue re-dissolved in anhydrous DMF (5 mL).Ammonium acetate (0.58 g, 7.5 mmol) was added and the mixture stirred atroom temperature over a weekend. Water was added and mixture extractedwith ether three times. The combined organic layer was washed withbrine, dried over anhydrous Na₂SO₄, filtered, concentrated, and purifiedon silica gel eluted with 8% EtOAc in hexane (v/v) to give 0.16 g of thedesired 5-(1-methylthioethyl)-2-pentafluoroethylpyridine (A) as brownishcolored oil in 12 percent yield. GC-MS: mass calcd for C₁₀H₁₁F₂N₃S [M]⁺271. Found 271.

To a stirred solution of the5-(1-methylthioethyl)-2-pentafluoro-ethylpyridine (A) (0.16 g, 0.6 mmol)and cyanamide (0.025 g, 0.6 mmol) in THF (3 mL) cooled to 0° C. wasadded iodobenzene diacetate (0.19 g, 0.6 mmol) in one portion and theresulting mixture was stirred at 0° C. for 2 h and then at roomtemperature overnight. The solvent was removed in vacuo and theresulting mixture was suspended in brine-saturated NaHCO₃ (9:1), whichwas then extracted with CH₂Cl₂-EtOAc (1:1, v/v) two times. The combinedorganic layer was dried over Na₂SO₄, filtered, concentrated, and driedto give 0.16 g of(1-{6-[pentafluoroethyl]pyridin-3-yl}ethyl)(methyl)-λ⁴-sulfanylidenecyanamide(B) as a brownish oil in 85 percent yield. LC-MS: mass calcd forC₁₁H₁₀F₅N₃S [M]⁺ 311.28. Found [M−1]⁺ 309.84.

To a stirred solution of the 80 percent 3-chloroperoxybenzoic acid (0.17g, ca 0.8 mmol) in ethanol (3 mL) cooled to 0° C. was added 20 percentaqueous potassium carbonate (1.0 mL, 1.5 mmol) and the resulting mixturewas stirred at 0° C. for 20 min. Then(1-{6[pentafluoro-ethyl]pyridin-3-yl}ethyl)(methyl)-λ⁴-sulfanylidenecyanamide(B) was added at once and the mixture was stirred at 0° C. for 1 h. Thereaction was quenched with a small spatula of solid sodium thiosulfate.Most of the solvent was evaporated and brine solution was added and themixture extracted with CH₂Cl₂ three times. The combined organic layerwas dried over Na₂SO₄, filtered and concentrated and the residue waspurified on silica gel using 10% acetone in CH₂Cl₂ (v/v) to give 0.089 gof[1-(6-pentafluoroethylpyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(7) as a white solid in 54% yield. LC-MS: mass calcd for C₁₀H₁₀F₅N₃OS[M]⁺ 327.28. Found [M−1]⁺ 325.83.

Example VII Preparation of2-trifluoromethyl-5-(1-{methyl(oxido)[oxido(oxo)hydrazono]-λ⁴-sulfanyl}ethyl)pyridine(8)

To a solution of 5-(1-methylthioethyl)-2-trifluoromethylpyridine (2.0 g,9 mmol) in CHCl₃ (20 mL) at 0° C. was added solution of mCPBA (2.1 g, 10mmol) in CHCl₃ (25 mL) over the course of 1.5 h. The solution wasstirred an additional 2 h, then it was concentrated and purified byflash chromatography (10 percent MeOH/CH₂Cl₂) to furnish541-methylsulfinyl-ethyl)-2-trifluoromethylpyridine (A) as a yellow oil(710 mg, 33 percent) and a ˜2:1 mixture of diastereomers. ¹H NMR (300MHz, CDCl₃) δ (major diastereomer) 8.7 (s, 1H), 7.8 (d, 1H), 7.7 (d,1H), 4.0 (q, 1H), 2.4 (s, 3H), 1.75 (d, 3H); (minor diastereomer) 8.6(s, 1H), 7.9 (d, 1H), 7.7 (d, 1H), 3.8 (q, 1H), 2.3 (s, 3H), 1.8 (d,3H); LC-MS (ELSD): mass calcd for C₉H₁₁F₃NOS [M+H]⁺, 238. Found 238.

To a solution of 5-(1-methylsulfinylethyl)-2-trifluoromethylpyridine (A)(600 mg, 2.5 mmol) in CHCl₃ (5 mL) at 0° C. was added sodium azide (260mg, 4.0 mmol) and H₂SO₄ (1 mL). The reaction was warmed to 55° C. untilgas evolution was observed, then it was cooled back down to roomtemperature overnight. The liquid was decanted into a separate flask andthe residual syrup was dissolved in H₂O, basified with Na₂CO₃ andextracted with CH₂Cl₂. The combined organic layers were dried overNa₂SO₄, concentrated and purified by flash chromatography to furnish5-[1-(methylsulfonimidoyl)ethyl]-2-trifluoromethylpyridine (B) as ayellow oil (130 mg, 20 percent) and a ˜1:1 mixture of diastereomers. ¹HNMR (300 MHz, CDCl₃) δ (mixture of diastereomer) 8.8 (d, 2H), 8.0 (dd,2H), 7.8 (d, 2H), 4.4 (m, 2H), 2.9 (s, 3H), 2.85 (s, 3H), 1.8 (m, 6H);LC-MS (ELSD): mass calcd for C₉H₁₁F₃N₂OS [M]⁺, 252. Found 252.

To a solution of5-[1-(methylsulfonimidoyl)ethyl]-2-trifluoromethylpyridine (B) (100 mg,0.4 mmol) in CH₂Cl₂ (2 mL) at 0° C. was added HNO₃ (16 μL, 0.4 mmol)dropwise. To the resulting suspension was added acetic anhydride (750μl) and concentrated H₂SO₄ (5 mL) and the mixture was heated to 40° C.The suspension slowly became homogeneous over the course of 15 min. Thesolvent was then removed and the crude residue was dissolved in H₂O,Solid Na₂CO₃ was added until pH 8 was reached and the aqueous phase wasextracted with CH₂Cl₂. The combined organic layers were dried overNa₂SO₄, concentrated and purified by flash chromatography to furnish2-trifluoromethyl-5-(1-{methyl(oxido)-[oxido(oxo)hydrazono]-λ⁴-sulfanyl}ethyl)pyridine(8) as a yellow oil (22 mg, 19 percent) and a 1:1 mixture ofdiastereomers. ¹H NMR (300 MHz, CDCl₃) δ (mixture of diastereomers) 8.8(d, 2H), 8.1 (m, 2H), 7.8 (m, 2H), 5.1 (q, 1H), 5.0 (q, 1H), 3.3 (s,3H), 3.25 (s, 3H), 2.0 (m, 6H); LC-MS (ELSD): mass calcd forC₉H₁₁F₃N₃O₃S [M+H]⁺, 298. Found 298.

Example VIII Preparation of[6-(1,1-difluoroethyl)pyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(9)

To a solution 5-methyl-2-acetylpyridine (9.9 g, 73.3 mmol) in moleculesieves-dried CH₂Cl₂ (150 mL) was added diethylamino sulfolnyltrifluoride(DAST) (25.8 g, 260 mmol) at room temperature and the mixture wasstirred at room temperature overnight. More DAST (12 g, 74 mmol) wasadded and the reaction continued for two more days after which anadditional DAST (3.8 g, 23 mmol) was added and the reaction continuedfor another 3 days. After the reaction was quenched slowly withsaturated NaHCO₃ at 0° C., the organic phase was separated, dried overNa₂SO₄, filtered, and concentrated. The residue was purified on silicagel eluted with 8% EtOAc in hexane to give 3.91 g of2-(1,1-difluoroethyl)-5-methylpyridine (A) as a light brownish oil in 34percent yield. GC-MS: mass calcd for C₈H₉F₂N [M]⁺ 157. Found 157.

A mixture of 2-(1,1-difluoroethyl)-5-methylpyridine (A) (2.0 g, 12.7mmol), N-bromosuccinimide (2.2 g, 12.7 mmol) and benzoylperoxide (0.15g, 0.63 mmol) in carbon tetrachloride (100 mL) was refluxed overnight.After the solid was removed by filtration, the filtrate wasconcentrated. The residue was re-dissolved in ethanol (40 mL) and sodiumthiomethoxide (1.33 g, 19 mmol) was added at room temperature andstirred for 3 h. The solvent was removed under reduced pressure and theremaining mixture was dissolved in CH₂Cl₂ and water. After separation,the organic layer was dried over Na₂SO₄, filtered and concentrated. Thecrude product 2-(1,1-difluoroethyl)-5-methylthiomethyl-pyridine (B) was94 percent pure on GC/MS, which was used directly for the next reactionwithout further purification. GC-MS: mass calcd for C₉H₁₁F₂NS [M]⁺ 203.Found 203.

To a stirred solution of2-(1,1-difluoroethyl)-5-methylthiomethylpyridine (B) (1.22 g. 6.0 mmol)and cyanamide (0.25 g, 6.0 mmol) in THF (7 mL) cooled to 0° C. was addediodobenzene diacetate (1.93 g, 6.0 mmol) in one portion and theresulting mixture was stirred at 0° C. for 1 h and then at roomtemperature for 2 h. The solvent was removed in vacuo and the resultingmixture was purified on silica gel using 60 percent acetone in hexane(v/v) to give 1.22 g of[(6-(1,1-difluoroethylpyridin-3-yl)methyl](methyl)-λ⁴-sulfanylidenecyanamide(C) (84 percent yield) as brownish oil which turned into a brownishsolid after standing in the refrigerator overnight. LC-MS: mass calcdfor C₁₀H₁₁F₂N₃S [M]⁺ 243.28. Found [M+1]⁺ 244.11.

To a 100 ml round bottom flask equipped with magnetic stirrer, additionfunnel, and thermometer was charged the sodium periodate (0.95 g, 4.44mmol) and water (12 mL). After the solid had dissolved, 15 mL of CH₂Cl₂was added followed by the ruthenium trichloride hydrate (0.033 g, 0.15mmol).[(6-(1,1-difluoroethylpyridin-3-yl)methyl](methyl)-λ⁴-sulfanylidenecyanamide(C) (0.72 g, 2.96 mmol) dissolved in 5 mL of CH₂Cl₂ was added dropwiseover a period of 30 min. The mixture was stirred rapidly at roomtemperature for 1.5 h and then filtered through a filtering paper toremove some insolubles. The mixture was then separated in separationfunnel after ethyl acetate was added to facilitate the separation. Theaqueous phase was extracted with CH₂Cl₂ twice. The combined organics waswashed with brine, dried over dry Na₂SO₄, filtered, concentrated, andbriefly purified on silica gel with 70 percent acetone in hexane to give0.652 g of the desired product[(6-(1,1-difluoroethylpyridin-3-yl)methyl](methyl)-oxidoλ⁴-sulfanylidenecyanamide (D) as a white solid in 87 percent yield.LC-MS: mass calcd for C₁₀H₁₁F₂N₃OS [M]⁺ 259.28. Found [M+1]⁺ 260.02.

To a solution of[(6-(1,1-difluoroethylpyridin-3-yl)methyl](methyl)-oxidoλ⁴-sulfanylidenecyanamide (D) (0.55 g, 2.0 mmol) and HMPA (0.09 mL, 0.55mmol) in 20 mL anhydrous THF was added 0.5 M potassiumbis(trimethylsilyl)amide in toluene (4.4 mL, 2.2 mmol) at −78° C.dropwise. After 45 min, iodomethane (0.14 mL, 2.2 mmol) was added in oneportion via a syringe. Ten minutes later, the temperature was allowed torise to 0° C. and mixture continued to stir for 1.5 h. The reaction wasquenched with saturated aqueous NH₄Cl, diluted with brine, extractedonce each with EtOAc and CH₂Cl₂. The combined organic layer was driedover Na₂SO₄, filtered, and concentrated. The residue was purified bypreparative HPLC to give 0.15 g of the desired[6-(1,1-difluoroethyl)pyridin-3-yl)ethyl](methyl)-oxido-λ⁴-sulfanylidenecyanamide(9) in 26 percent yield. LC-MS: mass calcd for C₁₁H₁₃F₂N₃OS [M]⁺ 273.31.Found [M+1]⁺ 274.21.

Further details regarding Examples I-VIII and other related compoundsare provided in U.S. Patent Application Publication 2007/0203191 A1, thecontents of which are incorporated herein by reference in theirentirety.

It should be appreciated that the compositions of this invention caninclude compounds that can exist as one or more stereoisomers. Forexample, in certain embodiments, the compositions include a mixture ofstereoisomers of a compound according to formula (I).

The various stereoisomers can include geometric isomers, diastereomersand enantiomers. Thus, the compositions of the present invention caninclude compounds of racemic mixtures, individual stereoisomers andoptically active mixtures. It will be appreciated by those skilled inthe art that one stereoisomer may be more active than the others.Individual stereoisomers and optically active mixtures may be obtainedby selective synthetic procedures, by conventional synthetic proceduresusing resolved starting materials or by conventional resolutionprocedures.

As a more particular example regarding stereoisomers, the{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl](methyl}oxido-λ⁴-sulfanylidenecyanamidecompound described in Example I includes four separate stereoisomers.These four stereoisomers define two pairs of diastereomers, which forthe purposes of this document are labeled as diastereomer groups (A) and(B). Diastereomer group (A) is defined by{(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxido-λ⁴-sulfanylidenecyanamide(A¹) and{(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxido-λ⁴-sulfanylidenecyanamide(A²) as represented below.

Diastereomer group (B) is defined by{(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxido-λ⁴-sulfanylidenecyanamide(B¹) and{(S)-1-[6-(triflouromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxido-λ⁴-sulfanylidenecyanamide(B²) as represented below.

For compositions including a mixture of stereoisomers of a compoundaccording to formula (I), conversion between the stereoisomers over timeis contemplated, thereby resulting in ratios between the stereoisomersthat are distinct from an initial ratio of the stereoisomers followingsynthesis of the compound. As a more particular example, following theinitial synthesis of the{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidecompound, diastereomer groups (A) and (B) are present in an approximate1:2 mixture. However, it has been observed that conversion betweendiastereomer groups (A) and (B) is possible over time, therebypresenting various chemical and physical stability issues with respectto a composition containing the{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidecompound.

Methods for selectively controlling the conversion between stereoisomersof a compound according to formula (I) in a composition including astereoisomeric mixture of the compound have now been surprisinglydiscovered. For example, in one form, a conversion between stereoisomerspresent in a composition at a first ratio is accelerated by heating thecomposition in a manner effective to yield a second ratio between thestereoisomers that is distinct from the first ratio. In one particularexample of this form, the heating is performed at a minimum of about 10°C. for at least about 4 hours. In another example, the heating isperformed at a minimum of about 20° C. for at least about 4 hours. Inyet another example, the heating is performed at a minimum of about 30°C. for at least about 4 hours. In still another example, the heating isperformed at a minimum of about 40° C. for at least about 4 hours. Inanother example, the heating is performed at a minimum of about 50° C.for at least about 4 hours. In yet another example, the heating isperformed at a minimum of about 60° C. for at least about 4 hours. In afurther example, the heating is performed at a minimum of about 70° C.for at least about 4 hours. In yet another example, the heating isperformed at a minimum of about 80° C. for at least about 4 hours. Instill another example, the heating is performed at a minimum of about90° C. for at least about 4 hours. In another example, the heating isperformed at a minimum of about 100° C. for at least about 4 hours.

Still, other variations in the temperature and time at which the heatingare performed are contemplated. For example, in one or more forms, it iscontemplated that the heating can be performed at one of thetemperatures specified above but for an alternative period of time, suchas from about 1 to about 100 hours. In a more particular form, theheating is performed at one of the above temperatures from about 2 toabout 90 hours. In another form, the heating is performed at one of theabove temperatures from about 4 to about 72 hours. In another variant,it is contemplated that the heating could be performed at a temperatureup to a point just below the degradation or melting point of thecompound according to formula (I) in the composition, thereby avoidingdegradation of the compound during heating. As one non-limiting example,when the composition includes the{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidecompound, the heating should be performed at a temperature less thanabout 128° C., which is the lower of the two melting points fordiastereomer groups A and B.

In another more particular example, the heating is performed from 23-70°C. for a period from 4-72 hours. In another example, the heating isperformed at 23° C. for at least about four hours. In yet anotherexample, the heating is performed at about 54° C. for a period from24-72 hours. In still another example, the heating is performed at about70° C. for a period from 4-72 hours. In a further variant of thisexample, the period is selected from one of 4, 8, 24 and 72 hours.Still, other variations in the temperature and time at which the heatingare performed are contemplated. For example, it is contemplated that asthe value for one of the temperature and period of time at which theheating is performed changes, the value for the other of the temperatureand period of time at which the heating is performed may also change.

In one or more forms, it is contemplated that the heating can beperformed before the formulation of the composition is complete. Forexample, in one embodiment, a composition that includes a stereoisomericmixture of a compound according to formula (I) and is substantially freeof other materials is heated to obtain the desired conversion betweenstereoisomers. One or more additional materials may then be added to thecomposition, such as a(n) phytologically-acceptable carrier, wettingagent, thickener, insecticide or antifreeze, just to name a fewpossibilities. In an alternative embodiment, a composition that includesa stereoisomeric mixture of a compound according to formula (I) and atleast one other insecticide, and is substantially free of othermaterials, is heated to obtain the desired conversion betweenstereoisomers. One or more additional materials may then be added to thecomposition, such as a phytologically-acceptable carrier, wetting agent,thickener or antifreeze, just to name a few examples. However, othervariations in the order in which the compositions described herein maybe prepared are contemplated. For example, in one or more forms, theformulation of the composition can be complete before it is heated. Inaddition to the foregoing, it should be appreciated that the compositioncan be subjected to further processing after the heating, including forexample, bead milling to reduce particle size of the composition.

In one embodiment, the stereoisomers of the compound according toformula (I) define two pairs of diastereomers and the heating convertsat least a portion of one pair of the diastereomers to the other pair ofthe diastereomers, thereby changing the ratio between the diastereomersof the compound present in the composition. In one more particular form,the ratio between the pairs of diastereomers after heating is at leastabout 3:1. In another form, the ratio between the pairs of diastereomersafter heating is greater than about 10:1. In yet another form, the ratiobetween the pairs of diastereomers after heating is greater than about20:1. In still another form, the ratio between the pairs ofdiastereomers after heating is greater than about 30:1. In another form,the ratio between the pairs of diastereomers after heating is greaterthan about 40:1. In a further form, the ratio between the pairs ofdiastereomers after heating is greater than about 50:1. In another form,the ratio between the pairs of diastereomers after heating is greaterthan about 60:1. In still another form, the ratio between the pairs ofdiastereomers after heating is greater than about 70:1. In yet anotherform, the ratio between the pairs of diastereomers after heating isgreater than about 80:1. In another form, the ratio between the pairs ofdiastereomers after heating is greater than about 90:1. In still anotherform, the ratio between the pairs of diastereomers after heating is atleast about 100:1. In another form, it is contemplated that only onepair of diastereomers remains after heating.

In another particular form, the ratio between the pairs of diastereomersafter heating is from about 3:1 to about 100:1. In yet another form, theratio between the pairs of diastereomers after heating is from about 3:1to about 50:1. In another form, the ratio between the pairs ofdiastereomers after heating is from about 3:1 to about 40:1. Still, inanother form, the ratio between the pairs of diastereomers after heatingis from about 3:1 to about 39:1. In yet another form, the ratio betweenthe pairs of diastereomers after heating is from about 19:1 to about39:1. In another form, the ratio between the pairs of diastereomersafter heating is from about 25:1 to about 39:1. Still, in other forms,the ratio between the pairs of diastereomers after heating is about39:1. It should be appreciated however that further variations of theratio between the pairs of the diastereomers are contemplated.

In another embodiment, a composition includes a compound according toformula (I) in a stereoisomeric mixture defined by two pairs ofdiastereomers. In one form, the mixture includes, based on the totalweight of the stereoisomeric mixture in the composition, a first pair ofdiastereomers from about 50 to about 98 weight percent and a second pairof diastereomers from about 2 to about 50 weight percent. In anotherform, the mixture includes, based on the total weight of thestereoisomeric mixture in the composition, a first pair of diastereomersfrom about 60 to about 98 weight percent and a second pair ofdiastereomers from about 2 to about 40 weight percent. In yet anotherform, the mixture includes, based on the total weight of thestereoisomeric mixture in the composition, a first pair of diastereomersfrom about 75 to about 98 weight percent and a second pair ofdiastereomers from about 2 to about 25 weight percent. In a furtherform, the mixture includes, based on the total weight of thestereoisomeric mixture in the composition, a first pair of diastereomersfrom about 85 to about 98 weight percent and a second pair ofdiastereomers from about 2 to about 15 weight percent. Still, in anotherform the mixture includes, based on the total weight of thestereoisomeric mixture in the composition, a first pair of diastereomersfrom about 90 to about 98 weight percent and a second pair ofdiastereomers from about 2 to about 10 weight percent. In another form,the mixture includes, based on the total weight of the stereoisomericmixture in the composition, a first pair of diastereomers from about 95to about 98 weight percent and a second pair of diastereomers from about2 to about 5 weight percent. In yet another form, the mixture includes,based on the total weight of the stereoisomeric mixture in thecomposition, a first pair of the diastereomers at about 99 weightpercent and a second pair of diastereomers at about 1 weight percent. Ina further form, the mixture includes, based on the total weight of thestereoisomeric mixture in the composition, about 100 weight percent of afirst pair of the diastereomers.

In one particular form of this embodiment, the compound according toformula (I) is{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamideand the first pair of stereoisomers is defined by{(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxido-λ⁴-sulfanylidenecyanamideand{(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxido-λ⁴-sulfanylidenecyanamideand the second pair of diastereomers is defined by{(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxido-λ⁴-sulfanylidenecyanamideand{(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxido-λ⁴-sulfanylidenecyanamide.In a further variation of this form, the stereoisomeric mixture havingone of the foregoing weight percentages of diastereomers is prepared byheating the composition at a temperature from about 20-70° C. for aperiod from about 4-72 hours. Additionally or alternatively, it iscontemplated that one or more other insecticides can be included in thisform. As one example, the composition can include a spinosyn, such asspinetoram, spinosad or mixtures thereof. When present, the compositioncan include a ratio, by weight, between{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxidoλ⁴-sulfanylidenecyanamideand the spinosyn from about 1:10 to about 10:1. In another form, thecomposition can include a ratio, by weight, between{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxidoλ⁴-sulfanylidenecyanamideand the spinosyn from about 1:5 to about 5:1. In yet another form, thecomposition can include a ratio, by weight, between{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxidoλ⁴-sulfanylidenecyanamideand the spinosyn from about 1:3 to about 3:1. In still another form, thecomposition can include a ratio, by weight, between{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamideand the spinosyn from about 2:1 to about 2.4:1.

While the mixture of{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamideand an insecticide, such as a spinosyn, has been described above, itshould be appreciated that in certain embodiments a composition caninclude any compound according to formula (I) and one or more otherinsecticides. For example, these compositions could include a compoundaccording to formula (I) and a spinosyn, such as spinetoram, spinosad ormixtures thereof. When present, these compositions can include a ratioby weight between the compound according to formula (I) and theinsecticide from about 1:10 to about 10:1. In another form, thesecompositions can include a ratio by weight between the compoundaccording to formula (I) and the insecticide from about 1:5 to about5:1. In still another form, these compositions can include a ratio byweight between the compound according to formula (I) and the insecticidefrom about 1:3 to about 3:1.

The compositions of this invention may also be provided with aphytologically-acceptable inert carrier in the form of sprays, topicaltreatments, gels, seed coatings, microcapsulations, systemic uptake,baits, eartags, boluses, foggers, fumigants aerosols, dusts and manyothers. Typically, formulations are applied as aqueous suspensions oremulsions. Such suspensions or emulsions are produced fromwater-soluble, water suspendable, or emulsifiable formulations which are(1) solids, usually known as wettable powders or water dispersiblegranules or (2) liquids, usually known as emulsifiable concentrates,aqueous emulsions, suspension concentrates and water suspended capsulescontaining the composition. As will be readily appreciated, any materialto which the composition can be added may be used, provided they yieldthe desired utility without significant interference with the activityof the composition as a pesticide.

Wettable powders, which may be compacted, extruded or processed througha dispersion in water followed by spray drying or fluid bedagglomeration to form water dispersible granules, comprise an intimatemixture of the composition, an inert carrier and surfactants. Theconcentration of the composition in the wettable powder is usually from10 percent to 90 percent by weight based on the total weight of thewettable powder, more preferably 25 weight percent to 75 weight percent.In the preparation of wettable powder formulations, the composition canbe compounded with any finely divided solid, such as prophyllite, talc,chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein,gluten, montmorillonite clays, diatomaceous earths, purified silicatesor the like. In such operations, the finely divided carrier andsurfactants are typically blended with the composition and milled.

Emulsifiable concentrates of the composition comprise a convenientconcentration, such as from 5 weight percent to 75 weight percent of thecomposition, in a suitable liquid, based on the total weight of theconcentrate. The composition is dissolved in an inert carrier, which iseither water, a water miscible solvent, a water immiscible solvent, or amixture thereof and emulsifiers. The concentrates may be diluted withwater and oil to form spray mixtures in the form of oil-in-wateremulsions. Useful organic solvents include aromatics, especially thehigh-boiling naphthalenic and olefinic portions of petroleum such asheavy aromatic naphtha. Other organic solvents may also be used, suchas, for example, terpenic solvents, including rosin derivatives,aliphatic ketones, such as cyclohexanone, and complex alcohols, such as2-ethoxyethanol.

Emulsifiers which can be advantageously employed herein can be readilydetermined by those skilled in the art and include various nonionic,anionic, cationic and amphoteric emulsifiers, or a blend of two or moreemulsifiers. Examples of nonionic emulsifiers useful in preparing theemulsifiable concentrates include the polyalkylene glycol ethers andcondensation products of alkyl and aryl phenols, aliphatic alcohols,aliphatic amines or fatty acids with ethylene oxide, propylene oxidessuch as the ethoxylated alkyl phenols and carboxylic esters solubilizedwith the polyol or polyokyalkylene. Cationic emulsifiers includequaternary ammonium compounds and fatty amine salts. Anionic emulsifiersinclude the oil-soluble salts (e.g., calcium) of alkylaryl sulphonicacids, oil soluble salts or sulfated polyglycol ethers and appropriatesalts of phosphated polyglycol ether.

Representative organic liquids which can be employed in preparing theemulsifiable concentrates of the composition are the aromatic liquidssuch as xylene, propyl benzene fractions; or mixed naphthalenefractions, mineral oils, substituted aromatic organic liquids such asdioctyl phthalate; kerosene; dialkyl amides of various fatty acids,particularly the dimethyl amides of fatty glycols and glycol derivativessuch as the n-butyl ether, ethyl ether or methyl ether of diethyleneglycol, and the methyl ether of triethylene glycol and the like.Mixtures of two or more organic liquids may also be employed in thepreparation of the emulsifiable concentrate. Preferred organic liquidsinclude xylene, and propyl benzene fractions, with propylbenzenefractions being most preferred. Surface-active emulsifying agents aretypically employed in liquid formulations and in an amount of from 0.1to 20 percent by weight based on the combined weight of the emulsifyingagent with the composition. The formulations comprising the compositionof the present invention can also contain other compatible additives,for example, miticides, insecticides, plant growth regulators, otherfungicides, and other biologically active compounds used in agriculture.

Aqueous suspensions comprise suspensions of the composition, dispersedin an aqueous vehicle at a concentration in the range from 5 to 50weight percent, based on the total weight of the aqueous suspension.Aqueous suspensions are prepared by vigorously mixing the composition ofthe present invention, or its solution, into a vehicle comprised ofwater and surfactants chosen from the same types discussed above. Othercomponents, such as inorganic salts and synthetic or natural gums, mayalso be added to increase the density and viscosity of the aqueousvehicle. Examples of aqueous suspensions include suspensions of oildroplets (EW's), solids (SC's), and capsules (CS's).

The composition can also be applied as granular formulations, which areparticularly useful for applications to the soil. Granular formulationsusually contain from 0.5 to 10 weight percent, based on the total weightof the granular formulation of the composition, dispersed in an inertcarrier which consists entirely or in large part of coarsely dividedinert material such as attapulgite, bentonite, diatomite, clay or asimilar inexpensive substance. Such formulations are usually prepared bydiluting the composition in a suitable solvent and applying it to agranular carrier which has been preformed to the appropriate particlesize, in the range of from 0.5 to 3 mm. A suitable solvent is a solventin which the compound is substantially or completely soluble. Suchformulations may also be prepared by making a dough or paste of thecarrier and the composition and solvent, and crushing and drying toobtain the desired granular particle.

The composition of the present invention can also be applied as a waterdispersible granule, or dry flowable formulation. Water dispersiblegranules typically contain from 10 to 70 percent of the composition,based on the total weight of the formulation. Such formulations aretypically obtained through mixing and/or spraying the mixture onto acarrier with the addition of a dispersing and/or wetting agent, andcombining with water to form a mixture suitable for further processingusing well known granulation technologies, such as pan granulation,extrusion, spray-drying, fluid bed agglomeration, and the like.

Dusts containing the composition can be prepared by intimately mixingthe composition with a suitable dusty agricultural carrier, such as, forexample, kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from 1 to 10 weight percent of the composition, basedon the total weight of the dust. Dusts may also be prepared byimpregnating the composition onto a carrier in a similar manner to thatdescribed for granules above.

The formulations of the present invention may additionally containadjuvant surfactants to enhance deposition, wetting and penetration ofthe composition onto the target crop and organism. These adjuvantsurfactants may optionally be employed as a component of the formulationor as a tank mix. The amount of adjuvant surfactant will typically varyfrom 0.01 to 1.0 percent by volume, based on a spray-volume of water,preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactantsinclude, but are not limited to ethoxylated nonyl phenols, ethoxylatedsynthetic or natural alcohols, salts of the esters or sulphosuccinicacids, ethoxylated organosilicones, ethoxylated fatty amines and blendsof surfactants with mineral or vegetable oils.

Example IX Preparation of Composition Including a Stereoisomeric Mixtureof{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamide

A 1 liter total volume (˜1100 g total weight) of a suspensionconcentrate product having a 240 g/L concentration of{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidewith an approximate 1:2 ratio between diastereomer groups A and B wasprepared by first adding deionized water to a clean beaker equipped witha mechanical stirrer. The following ingredients were then added to thebeaker, in no particular, under continued stirring: 3.5 g of Agnique®DFM 112S, a silicon based defoamer available commercially from theCognis Group, headquartered in Monheim, Germany; 20 g of Tersperse®2500, a polymeric surfactant commercially available from HuntsmanPerformance Products, 10003 Woodloch Forest Drive, The Woodlands, Tex.77380; 30 g of Morwet® D-360, a surfactant commercially available fromAkzo Nobel Surfactants, 525 W. Van Buren St., Chicago, Ill. 60607; 20 gof Ethylan® NS 500 LQ, a surfactant commercially available from AkzoNobel Surfactants, 525 W. Van Buren St., Chicago, Ill. 60607; 40 g ofpropylene glycol; 1 g of Proxel® GXL, a microbiostat solutioncommercially available from Arch Chemicals, Inc., 1955 Lake Drive, Suite100, Smyrna, Ga. 30080. 240 g of{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidewas then added to the beaker, followed by the addition of 10 g ofAvicel® CL-611, a stabilizer commercially available from FMC BioPolymer,1735 Market Street, Philadelphia, Pa. 19103, and 2 g of Kelzan, axanthan gum commercially available from CP Kelco, 1000 Parkwood Circle,Suite 1000, Atlanta, Ga. 30339. The ingredients were stirred until ahomogeneous mixture was obtained. The mixture was then milled with abead mill down to an average particle size of 3-5 μm. The finalformulation of this suspension concentrate product is set forth in Table1.

TABLE 1 Ingredients g/L {1-[6-(trifluoromethyl)pyridin- 2403-yl]ethyl}(methyl)oxido-λ⁴- sulfanylidenecyanamide Agnique ® DFM 112S3.5 Avicel ® CL-611 10 Tersperse ® 2500 20 Morwet ® D-360 30 Ethylan ®NS 500 LQ 20 Propylene glycol 40 Proxel ® GXL 1 Kelzan ® 2 Water balance

A composition having a 160 mL total volume was prepared by combining 80mL of the suspension concentrate product described above having a 240g/L concentration of{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamideand 80 mL of Radiant® SC, an insecticide formulation having a 120 g/Lconcentration of spinetoram and being commercially available from DowAgroSciences, LLC, 9330 Zionsville Road, Indianapolis, Ind. 46268. Thecomposition was thoroughly mixed until a homogenous consistency wasobtained. Sixteen individual 10 mL samples (samples (i)-(xvi)) of thecomposition were then heated in an oven in accordance with the time andtemperature parameters set forth in Table 2 below.

TABLE 2 Heating Parameters 4 hrs 8 hrs 24 hrs 72 hrs 23° C. (i) (v) (ix)(xiii) 40° C. (ii) (vi) (x) (xiv) 54° C. (iii) (vii) (xi) (xv) 70° C.(iv) (viii) (xii) (xvi)Upon expiration of the respective time periods set forth in Table 2, thesamples were removed from the oven and subsequently assayed bychromatography to measure the ratio between diastereomer groups A and Bof{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidein each sample after heating. The results of the chromatography analysisare provided in Table 3, which also indicates the pH of each sample andthe percent by weight, based on the total weight of the respectivesample, of{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamideand spinetoram.

TABLE 3 Diastereomer ratios of {1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamide in samples (i)-(xvi)after heating. {1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴- sulfanylidenecyanamide SpinetoramDiastereomer Diastereomer Total Assay, Total Assay, Sample pH (A)% (B)%% w/w % w/w (i) 7.23 50.74 49.26 10.967 4.562 (ii) 7.20 53.33 46.6710.981 4.574 (iii) 7.23 62.63 37.37 10.913 4.567 (iv) 7.28 94.98 5.0210.722 4.557 (v) 7.23 50.95 49.05 10.953 4.564 (vi) 7.18 55.26 44.7410.844 4.520 (vii) 7.21 74.02 25.98 10.786 4.548 (viii) 7.23 95.55 4.4510.677 4.556 (ix) 7.20 51.52 48.48 10.975 4.569 (x) 7.16 63.31 36.6910.887 4.576 (xi) 7.16 97.03 2.97 10.697 4.577 (xii) 7.21 95.18 4.8210.710 4.541 (xiii) 7.16 53.38 46.62 11.035 4.595 (xiv) 7.15 86.06 13.9410.832 4.598 (xv) 7.17 97.51 2.49 10.768 4.613 (xvi) 7.24 96.15 3.8510.766 4.614

It should be appreciated that the foregoing Examples are forillustration purposes and are not intended to be construed as limitingthe invention disclosed in this document to only the embodimentsdisclosed in these examples. For example, it is contemplated that the{1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ⁴-sulfanylidenecyanamidecompound in the exemplary composition could be replaced with one or amixture of the compounds according to formula (I). Similarly, it iscontemplated that the exemplary composition could be prepared with oneor more co-ingredients in addition to or in lieu of spinetoram, oralternatively, may be free from any co-ingredients.

Insecticide Utility

The compositions disclosed in this document are useful for the controlof invertebrates including insects. Therefore, the present inventionalso is directed to a method for inhibiting an insect which comprisesapplying an insect-inhibiting amount of the composition to a locus ofthe insect, to the area to be protected, or directly on the insect to becontrolled. The compositions of the invention may also be used tocontrol other invertebrate pests such as mites and nematodes.

The “locus” of insects or other pests is a term used herein to refer tothe environment in which the insects or other pests live or where theireggs are present, including the air surrounding them, the food they eat,or objects which they contact. For example, insects which eat, damage orcontact edible, commodity, ornamental, turf or pasture plants can becontrolled by applying the compositions to the seed of the plant beforeplanting, to the seedling, or cutting which is planted, the leaves,stems, fruits, grain, and/or roots, or to the soil or other growthmedium before or after the crop is planted. Protection of these plantsagainst virus, fungus or bacterium diseases may also be achievedindirectly through controlling sap-feeding pests such as whitefly, planthopper, aphid and spider mite. Such plants include those which are bredthrough conventional approaches and which are genetically modified usingmodern biotechnology to gain insect-resistant, herbicide-resistant,nutrition-enhancement, and/or any other beneficial traits.

It is contemplated that the compositions might also be useful to protecttextiles, paper, stored grain, seeds and other foodstuffs, houses andother buildings which may be occupied by humans and/or companion, farm,ranch, zoo, or other animals, by applying an active composition to ornear such objects. Domesticated animals, buildings or human beings mightbe protected with the compositions by controlling invertebrate and/ornematode pests that are parasitic or are capable of transmittinginfectious diseases. Such pests include, for example, chiggers, ticks,lice, mosquitoes, flies, fleas and heartworms. Nonagronomic applicationsalso include invertebrate pest control in forests, in yards, along roadsides and railroad right of way.

The term “inhibiting an insect” refers to a decrease in the numbers ofliving insects, or a decrease in the number of viable insect eggs. Theextent of reduction accomplished by a composition depends, of course,upon the application rate of the composition, the particular compositionused, and the target insect species. At least an inactivating amountshould be used. The term “insect-inactivating amount” is used todescribe the amount, which is sufficient to cause a measurable reductionin the treated insect population. Generally an amount in the range fromabout 1 to about 1000 ppm by weight active compound is used. Forexample, insects or other pests which can be inhibited include, but arenot limited to:

Lepidoptera—Heliothis spp., Helicoverpa spp., Spodoptera spp., Mythimnaunipuncta, Agrotis Ipsilon, Earias spp., Euxoa auxiliaris, Trichoplusiani, Anticarsia gemmalalis, Rachiplusia nu, Plutella xylostella, Chilospp., Scirpophaga incertulas, Sesamia inferens, Cnaphalocrocismedinalis, Ostrinia nubilalis, Cydia pomonella, Carposina niponensis,Adoxophyes orana, Archips argyrospilus, Pandemis heparana, Epinotiaaporema, Eupoecilia ambiguella, Lobesia botrana, Polychrosis viteana,Pectinophora gossypiella, Pieris rapae, Phyllonorycter spp., Leucopteramalifoliella, Phyllocnisitis citrella

Coleoptera—Diabrotica spp., Leptinotarsa decemlineata, Oulema oryzae,Anthonomus grandis, Lissorhoptrus oryzophilus, Agriotes spp., Melanotuscommunis, Popillia japonica, Cyclocephala spp., Tribolium spp.

Homoptera—Aphis spp., Myzus persicae, Rhopalosiphum spp., Dysaphisplantaginea, Toxoptera spp., Macrosiphum euphorbiae, Aulacorthum solani,Sitobion avenae, Metopolophium dirhodum, Schizaphis graminum,Brachycolus noxius, Nephotettix spp., Nilaparvata lugens, Sogatellafurcifera, Laodelphax striatellus, Bernisia tabaci, Trialeurodesvaporariorum, Aleurodes proletella, Aleurothrixus floccosus,Quadraspidiotus perniciosus, Unaspis yanonensis, Ceroplastes rubens,Aonidiella aurantil

Hemiptera—Lygus spp., Eurygaster maura, Nezara viridula, Piezodorusguildingi, Leptocorisa varicornis, Cimex lectularius, Cimex hemipterus

Thysanoptera—Frankliniella spp., Thrips spp., Scirtothrips dorsalis

Isoptera—Reticulitermes flavipes, Coptotermes formosanus, Reticulitermesvirginicus, Heterotermes aureus, Reticulitermes hesperus, Coptotermesfrenchii, Shedorhinotermes spp., Reticulitermes santonensis,Reticulitermes grassei, Reticulitermes banyulensis, Reticulitermessperatus, Reticulitermes hageni, Reticulitermes tibialis, Zootermopsisspp., Incisitermes spp., Marginitermes spp., Macrotermes spp.,Microcerotermes spp., Microtermes spp.

Diptera—Liriomyza spp., Musca domestica, Aedes spp., Culex spp.,Anopheles spp., Fannia spp., Stomoxys spp.

Hymenoptera—Iridomyrmex humilis, Solenopsis spp., Monomorium pharaonis,Atta spp., Pogonomyrmex spp., Camponotus spp., Monomorium spp., Tapinomasessile, Tetramorium spp., Xylocapa spp., Vespula spp., Polistes spp.

Mallophaga (chewing lice)

Anoplura (sucking lice)—Pthirus pubis, Pediculus spp.

Orthoptera (grasshoppers, crickets)—Melanoplus spp., Locusta migratoria,Schistocerca gregaria, Gryllotalpidae (mole crickets).

Blattoidea (cockroaches)—Blatta orientalis, Blattella germanica,Periplaneta americana, Supella longipalpa, Periplaneta australasiae,Periplaneta brunnea, Parcoblalta pennsylvanica, Periplaneta fuliginosa,Pycnoscelus surinamensis,

Siphonaptera—Ctenophalides spp., Pulex irritans

Acari—Tetranychus spp., Panonychus spp., Eotetranychus carpini,Phyllocoptruta oleivora, Aculus pelekassi, Brevipalpus phoencis,Boophilus spp., Dermacentor variabilis, Rhipicephalus sanguineus,Amblyomma americanum, Ixodes spp., Notoedres cati, Sarcoptes scabiei,Dermatophagoides spp.

Nematoda—Dirofilaria immitis, Meloidogyne spp., Heterodera spp.,Hoplolaimus columbus, Belonolaimus spp., Pratylenchus spp., Rotylenchusreniformis, Criconemella ornata, Ditylenchus spp., Aphelenchoidesbesseyi, Hirschmanniella spp.

The actual amount of composition to be applied to loci of insects andmites is not critical and can readily be determined by those skilled inthe art in view of the examples above. In general, concentrations from10 ppm to 5000 ppm by weight of compound are expected to provide goodcontrol. With many of the compounds, concentrations from 100 to 1500 ppmwill suffice.

The locus to which a composition is applied can be any locus inhabitedby an insect or mite, for example, vegetable crops, fruit and nut trees,grape vines, ornamental plants, domesticated animals, the interior orexterior surfaces of buildings, and the soil around buildings.

Because of the unique ability of insect eggs to resist toxicant action,repeated applications may be desirable to control newly emerged larvae,as is true of other known insecticides and acaricides.

Systemic movement of compositions of the invention in plants may beutilized to control pests on one portion of the plant by applying thecompositions to a different portion of it. For example, control offoliar-feeding insects can be controlled by drip irrigation or furrowapplication, or by treating the seed before planting. Seed treatment canbe applied to all types of seeds, including those from which plantsgenetically transformed to express specialized traits will germinate.Representative examples include those expressing proteins toxic toinvertebrate pests, such as Bacillus thuringiensis or other insecticidalproteins, those expressing herbicide resistance, such as “RoundupReady®” seed, or those with “stacked” foreign genes expressinginsecticidal proteins, herbicide resistance, nutrition-enhancementand/or any other beneficial traits.

The composition can also be provided as an insecticidal bait formulationincluding attractants and/or feeding stimulants that may be used toincrease efficacy of the compositions against insect pest in a devicesuch as trap, bait station, and the like. The bait formulation isusually a solid, semi-solid (including gel) or liquid bait matrixincluding the stimulants and one or more non-microencapsulated ormicroencapsulated insecticides in an amount effective to act as killagents.

The compositions of the present invention are often applied inconjunction with one or more other insecticides or fungicides orherbicides to obtain control of a wider variety of pests diseases andweeds. When used in conjunction with other insecticides or fungicides orherbicides, the presently claimed compositions can be formulated withthe other insecticides or fungicides or herbicide, tank mixed with theother insecticides or fungicides or herbicides, or applied sequentiallywith the other insecticides or fungicides or herbicides.

Some of the insecticides that can be employed beneficially incombination with the compositions of the present invention include:antibiotic insecticides such as allosamidin and thuringiensin;macrocyclic lactone insecticides such as spinosad, spinetoram, and otherspinosyns including the 21-butenyl spinosyns and their derivatives;avermectin insecticides such as abamectin, doramectin, emamectin,eprinomectin, ivermectin and selamectin; milbemycin insecticides such aslepimectin, milbemectin, milbemycin oxime and moxidectin; arsenicalinsecticides such as calcium arsenate, copper acetoarsenite, copperarsenate, lead arsenate, potassium arsenite and sodium arsenite;biological insecticides such as Bacillus popilliae, B. sphaericius, B.thurinigiensis subsp. aizawai, B. thuringiensis subsp. kurstaki, B.thuriugiensis subsp. tenebrionis, Beauveria bassiana, Cydia pomonellagranulosis virus, Douglas fir tussock moth NPV, gypsy moth NPV,Helicoverpa zea NPV, Indian meal moth granulosis virus, Metarhiziumanisopliae, Nosema locustae, Paecilomyces fumosoroseus, P. lilacinus,Photorhabdus luminescens, Spodoptera exigua NPV, trypsin modulatingoostatic factor, Xenorhabdus nematophilus, and X. bovienii; plantincorporated protectant insecticides such as Cry1Ab, Cry1Ac, Cry1F,Cry1A.105, Cry2Ab2, Cry3A, mir Cry3A, Cry3Bbl, Cry34, Cry35, and VIP3A;botanical insecticides such as anabasine, azadirachtin, d-limonene,nicotine, pyrethrins, cinerins, cinerin I, cinerin II, jasmolin I,jasmolin II, pyrethrin I, pyrethrin II, quassia, rotenone, ryania andsabadilla; carbamate insecticides such as bendiocarb and carbaryl;benzofuranyl methylcarbamate insecticides such as benfuracarb,carbofuran, carbosulfan, decarbofuran and furathiocarb;dimethylcarbamate insecticides dimitan, dimetilan, hyquincarb andpirimicarb; oxime carbamate insecticides such as alanycarb, aldicarb,aldoxycarb, butocarboxim, butoxycarboxim, methomyl, nitrilacarb, oxamyl,tazimcarb, thiocarboxime, thiodicarb and thiofanox; phenylmethylcarbamate insecticides such as allyxycarb, aminocarb, bufencarb,butacarb, carbanolate, cloethocarb, dicresyl, dioxacarb, EMPC,ethiofencarb, fenethacarb, fenobucarb, isoprocarb, methiocarb,metolcarb, mexacarbate, promacyl, promecarb, propoxur, trimethacarb, XMCand xylylcarb; dinitrophenol insecticides such as dinex, dinoprop,dinosam and DNOC; fluorine insecticides such as bariumhexafluorosilicate, cryolite, sodium fluoride, sodium hexafluorosilicateand sulfluramid; formamidine insecticides such as amitraz,chlordimeform, formetanate and formparanate; fumigant insecticides suchas acrylonitrile, carbon disulfide, carbon tetrachloride, chloroform,chloropicrin, para-dichlorobenzene, 1,2-dichloropropane, ethyl formate,ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogencyanide, iodomethane, methyl bromide, methylchloroform, methylenechloride, naphthalene, phosphine, sulfuryl fluoride andtetrachloroethane; inorganic insecticides such as borax, calciumpolysulfide, copper oleate, mercurous chloride, potassium thiocyanateand sodium thiocyanate; chitin synthesis inhibitors such asbistrifluoron, buprofezin, chlorfluazuron, cyromazine, diflubenzuron,flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron,noviflumuron, penfluoron, teflubenzuron and triflumuron; juvenilehormone mimics such as epofenonane, fenoxycarb, hydroprene, kinoprene,methoprene, pyriproxyfen and triprene; juvenile hormones such asjuvenile hormone I, juvenile hormone II and juvenile hormone III;moulting hormone agonists such as chromafenozide, halofenozide,methoxyfenozide and tebufenozide; moulting hormones such as α-ecdysoneand ecdysterone; moulting inhibitors such as diofenolan; precocenes suchas precocene I, precocene II and precocene III; unclassified insectgrowth regulators such as dicyclanil; nereistoxin analogue insecticidessuch as bensultap, cartap, thiocyclam and thiosultap; nicotinoidinsecticides such as flonicamid; nitroguanidine insecticides such asclothianidin, dinotefuran, imidacloprid and thiamethoxam; nitromethyleneinsecticides such as nitenpyram and nithiazine; pyridylmethylamineinsecticides such as acetamiprid, imidacloprid, nitenpyram andthiacloprid; organochlorine insecticides such as bromo-DDT, camphechlor,DDT, pp′-DDT, ethyl-DDD, HCH, gamma-HCH, lindane, methoxychlor,pentachlorophenol and TDE; cyclodiene insecticides such as aldrin,bromocyclen, chlorbicyclen, chlordane, chlordecone, dieldrin, dilor,endosulfan, endrin, HEOD, heptachlor, HHDN, isobenzan, isodrin, kelevanand mirex; organophosphate insecticides such as bromfenvinfos,chlorfenvinphos, crotoxyphos, dichlorvos, dicrotophos, dimethylvinphos,fospirate, heptenophos, methocrotophos, mevinphos, monocrotophos, naled,naftalofos, phosphamidon, propaphos, TEPP and tetrachlorvinphos;organothiophosphate insecticides such as dioxabenzofos, fosmethilan andphenthoate; aliphatic organothiophosphate insecticides such as acethion,amiton, cadusafos, chlorethoxyfos, chlormephos, demephion, demephion-O,demephion-S, demeton, demeton-O, demeton-S, demeton-methyl,demeton-O-methyl, demeton-S-methyl, demeton-5-methylsulphon, disulfoton,ethion, ethoprophos, PSP, isothioate, malathion, methacrifos,oxydemeton-methyl, oxydeprofos, oxydisulfoton, phorate, sulfotep,terbufos and thiometon; aliphatic amide organothiophosphate insecticidessuch as amidithion, cyanthoate, dimethoate, ethoate-methyl, formothion,mecarbam, omethoate, prothoate, sophamide and vamidothion; oximeorganothiophosphate insecticides such as chlorphoxim, phoxim andphoxim-methyl; heterocyclic organothiophosphate insecticides such asazamethiphos, coumaphos, coumithoate, dioxathion, endothion, menazon,morphothion, phosalone, pyraclofos, pyridaphenthion and quinothion;benzothiopyran organothiophosphate insecticides such as dithicrofos andthicrofos; benzotriazine organothiophosphate insecticides such asazinphos-ethyl and azinphos-methyl; isoindole organothiophosphateinsecticides such as dialifos and phosmet; isoxazole organothiophosphateinsecticides such as isoxathion and zolaprofos; pyrazolopyrimidineorganothiophosphate insecticides such as chlorprazophos and pyrazophos;pyridine organothiophosphate insecticides such as chlorpyrifos andchlorpyrifos-methyl; pyrimidine organothiophosphate insecticides such asbutathiofos, diazinon, etrimfos, lirimfos, pirimiphos-ethyl,pirimiphos-methyl, primidophos, pyrimitate and tebupirimfos; quinoxalineorganothiophosphate insecticides such as quinalphos andquinalphos-methyl; thiadiazole organothiophosphate insecticides such asathidathion, lythidathion, methidathion and prothidathion; triazoleorganothiophosphate insecticides such as isazofos and triazophos; phenylorganothiophosphate insecticides such as azothoate, bromophos,bromophos-ethyl, carbophenothion, chlorthiophos, cyanophos, cythioate,dicapthon, dichlofenthion, etaphos, famphur, fenchlorphos, fenitrothionfensulfothion, fenthion, fenthion-ethyl, heterophos, jodfenphos,mesulfenfos, parathion, parathion-methyl, phenkapton, phosnichlor,profenofos, prothiofos, sulprofos, temnephos, trichlormetaphos-3 andtrifenofos; phosphloiate insecticides such as butonate and trichlorfon;phosphonothioate insecticides such as mecarphon; phenylethylphosplionotliioate insecticides such as fonofos and trichloronat;phenyl phenylphosphonothioate insecticides such as cyanofenphos, EPN andleptophos; phosphoramidate insecticides such as crufomate, fenamiphos,fosthietan, mephosfolan, phosfolan and pirimetaphos;phosphoramidothioate insecticides such as acephate, isocarbophos,isofenphos, methamidophos and propetamphos; phosphorodiamideinsecticides such as dimefox, mazidox, mipafox and schradan; oxadiazineinsecticides such as indoxacarb; phthalimide insecticides such asdialifos, phosmet and tetramethrin; pyrazole insecticides such asacetoprole, ethiprole, fipronil, pyrafluprole, pyriprole, tebufenpyrad,tolfenpyrad and vaniliprole; pyrethroid ester insecticides such asacrinathrin, allethrin, bioallethrin, barthrin, bifenthrin,bioethanomethrin, cyclethrin, cycloprothrin, cyfluthrin,beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin,cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin,zeta-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, dimethrin,empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate,esfenvalerate, flucythrinate, fluvalinate, tau-fluvalinate, furethrin,imiprothrin, metofluthrin, permethrin, biopermethrin, transpermethrin,phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin,bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin,tralomethrin and transfluthrin; pyrethroid ether insecticides such asetofenprox, flufenprox, halfenprox, protrifenbute and silafluofen;pyrimidinamine insecticides such as flufenerim and pyrimidifen; pyrroleinsecticides such as chlorfenapyr; tetronic acid insecticides such asspirodiclofen, spiromesifen and spirotetramat; thiourea insecticidessuch as diafenthiuron; urea insecticides such as flucofuron andsulcofuron; and unclassified insecticides such as AKD-3088, closantel,crotamiton, cyflumetofen, E2Y45, EXD, fenazaflor, fenazaquin,fenoxacrim, fenpyroximate, FKI-1033, flubendiamide, HGW86,hydramethylnon, IKI-2002, isoprothiolane, malonoben, metaflumizone,metoxadiazone, nifluridide, NNI-9850, NNI-0101, pymetrozine, pyridaben,pyridalyl, Qcide, rafoxanide, rynaxypyr, SYJ-159, triarathene andtriazamate and any combinations thereof.

Some of the fungicides that can be employed beneficially in combinationwith the compositions of the present invention include:2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,8-hydroxyquinoline sulfate, Ampelomyces, quisqualis, azaconazole,azoxystrobin, Bacillus subtilis, benalaxyl, benomyl,benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt,bicarbonates, biphenyl, bismerthiazol, bitertanol, blasticidin-S, borax,Bordeaux mixture, boscalid, bromuconazole, bupirimate, calciumpolysulfide, captafol, captan, carbendazim, carboxin, carpropamid,carvone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans,copper hydroxide, copper octanoate, copper oxychloride, copper sulfate,copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid,cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammoniumethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet,diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion,diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M,dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorphacetate, dodine, dodine free base, edifenphos, epoxiconazole, ethaboxam,ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fentin, fentin acetate, fentin hydroxide,ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide,fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide,flutolanil, flutriafol, folpet, formaldehyde, fosetyl,fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine,guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol,imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadinetriacetate, iminoctadine tris(albesilate), ipconazole, iprobenfos,iprodione, iprovalicarb, isoprothiolane, kasugamycin, kasugamycinhydrochloride hydrate, kresoxim-methyl, mancopper, mancozeb, maneb,mepanipyrim, mepronil, mercuric chloride, mercuric oxide, mercurouschloride, metalaxyl, mefenoxam, metalaxyl-M, metam, metam-ammonium,metam-potassium, metam-sodium, metconazole, methasulfocarb, methyliodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone,mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol,octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl,oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate,penconazole, pencycuron, pentachlorophenol, pentachlorophenyl laurate,penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide,picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate,potassium hydroxyquinoline sulfate, probenazole, prochloraz,procymidone, propamocarb, propamocarb hydrochloride, propiconazole,propineb, proquinazid, prothioconazole, pyraclostrobin, pyrazophos,pyributicarb, pyrifenox, pyrimethanil, pyroquilon, quinoclamine,quinoxyfen, quintozene, Reynoutria sachalinensis extract, silthiofam,simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodiumpentachlorophenoxide, spiroxamine, sulfur, SYP-Z071, tar oils,tebuconazole, tecnazene, tetraconazole, thiabendazole, thifluzamide,thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid,triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph,trifloxystrobin, triflumizole, triforine, triticonazole, validamycin,vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusariumoxysporum, Gliocladium spp., Phlebiopsis gigantean, Streptomycesgriseoviridis, Trichoderma spp.,(RS)-N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate,1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide,2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine,4-(2-nitroprop-1-enyl)phenyl thiocyanateme: ampropylfos, anilazine,azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox,bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmiumcalcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone,chloraniformethan, chlorfenazole, chlorquinox, climbazole, copperbis(3-phenylsalicylate), copper zinc chromate, cufraneb, cuprichydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram,decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol,dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin,drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf,fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole,furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin,halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos,isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam,methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride,myclozolin, N-3,5-dichlorophenyl-succinimide,N-3-nitrophenylitaconimide, natamycin,N-ethylmercurio-4-toluenesulfonanilide, nickelbis(dimethyldithiocarbamate), OCH, phenylmercurydimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb;prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor,pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole,rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor,thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid,triamiphos, triarimol, triazbutil, trichlamide, urbacid, XRD-563, andzarilamid, and any combinations thereof.

Some of the herbicides that can be employed in conjunction with thecompositions of the present invention include: amide herbicides such asallidochlor, beflubutamid, benzadox, benzipram, bromobutide,cafenstrole, CDEA, chlorthiamid, cyprazole, dimethenamid,dimethenamid-P, diphenamid, epronaz, etnipromid, fentrazamide, flupoxam,fomesafen, halosafen, isocarbamid, isoxaben, napropamide, naptalam,pethoxamid, propyzamide, quinonamid and tebutam; anilide herbicides suchas chloranocryl, cisanilide, clomeprop, cypromid, diflufenican,etobenzanid, fenasulam, flufenacet, flufenican, mefenacet, mefluidide,metamifop, monalide, naproanilide, pentanochlor, picolinafen andpropanil; arylalanine herbicides such as benzoylprop, flamprop andflamprop-M; chloroacetanilide herbicides such as acetochlor, alachlor,butachlor, butenachlor, delachlor, diethatyl, dimethachlor, metazachlor,metolachlor, S-metolachlor, pretilachlor, propachlor, propisochlor,prynachlor, terbuchlor, thenylchlor and xylachlor; sulfonanilideherbicides such as benzofluor, perfluidone, pyrimisulfan and profluazol;sulfonamide herbicides such as asulam, carbasulam, fenasulam andoryzalin; antibiotic herbicides such as bilanafos; benzoic acidherbicides such as chloramben, dicamba, 2,3,6-TBA and tricamba;pyrimidinyloxybenzoic acid herbicides such as bispyribac andpyriminobac; pyrimidinylthiobenzoic acid herbicides such as pyrithiobac;phthalic acid herbicides such as chlorthal; picolinic acid herbicidessuch as aminopyralid, clopyralid and picloram; quinolinecarboxylic acidherbicides such as quinclorac and quinmerac; arsenical herbicides suchas cacodylic acid, CMA, DSMA, hexaflurate, MAA, MAMA, MSMA, potassiumarsenite and sodium arsenite; benzoylcyclohexanedione herbicides such asmesotrione, sulcotrione, tefuryltrione and tembotrione; benzofuranylalkylsulfonate herbicides such as benfuresate and ethofumesate;carbamate herbicides such as asulam, carboxazole chlorprocarb,dichlormate, fenasulam, karbutilate and terbucarb; carbanilateherbicides such as barban, BCPC, carbasulam, carbetamide, CEPC,chiorbufam, chlorpropham, CPPC, desmedipham, phenisopham, phenmedipham,phenmedipham-ethyl, propham and swep; cyclohexene oxime herbicides suchas alloxydim, butroxydim, clethodim, cloproxydim, cycloxydim,profoxydim, sethoxydim, tepraloxydim and tralkoxydim;cyclopropylisoxazole herbicides such as isoxachlortole and isoxaflutole;dicarboximide herbicides such as benzfendizone, cinidon-ethyl, flumezin,flumiclorac, flumioxazin and flumipropyn; dinitroaniline herbicides suchas benfluralin, butralin, dinitramine, ethalfluralin, fluchloralin,isopropalin, methalpropalin, nitralin, oryzalin, pendimethalin,prodiamine, profluralin and trifluralin; dinitrophenol herbicides suchas dinofenate, dinoprop, dinosam, dinoseb, dinoterb, DNOC, etinofen andmedinoterb; diplhenyl ether herbicides such as ethoxyfen; nitrophenylether herbicides such as acifluorfen, aclonifen, bifenox,chlomethoxyfen, chlornitrofen, etnipromid, fluorodifen, fluoroglycofen,fluoronitrofen, fomesafen, furyloxyfen, halosafen, lactofen, nitrofen,nitrofluorfen and oxyfluorfen; dithiocarbamate herbicides such asdazomet and metam; halogenated aliphatic herbicides such as alorac,chloropon, dalapon, flupropanate, hexachloroacetone, iodomethane, methylbromide, monochloroacetic acid, SMA and TCA; imidazolinone herbicidessuch as imazamethabenz, imazamox, imazapic, imazapyr, imazaquin andimazethapyr; inorganic herbicides such as ammonium sulfamate, borax,calcium chlorate, copper sulfate, ferrous sulfate, potassium azide,potassium cyanate, sodium azide, sodium chlorate and sulfuric acid;nitrile herbicides such as bromobonil, bromoxynil, chloroxynil,dichlobenil, iodobonil, ioxynil and pyraclonil; organophosphorusherbicides such as amiprofos-methyl, anilofos, bensulide, bilanafos,butamifos, 2,4-DEP, DMPA, EBEP, fosamine, glufosinate, glyphosate andpiperophos; phenoxy herbicides such as bromofenoxim, clomeprop, 2,4-DEB,2,4-DEP, difenopenten, disul, erbon, etnipromid, fenteracol andtrifopsime; phenoxyacetic herbicides such as 4-CPA, 2,4-D, 3,4-DA, MCPA,MCPA-thioethyl and 2,4,5-T; phenoxybutyric herbicides such as 4-CPB,2,4-DB, 3,4-DB, MCPB and 2,4,5-TB; phenoxypropionic herbicides such ascloprop, 4-CPP, dichlorprop, dichlorprop-P, 3,4-DP, fenoprop,mecopropand mecoprop-P; aryloxyphenoxypropionic herbicides such aschlorazifop, clodinafop, clofop, cyhalofop, diclofop, fenoxaprop,fenoxaprop-P, fenthiaprop, fluazifop, fluazifop-P, haloxyfop,haloxyfop-P, isoxapyrifop, metamifop, propaquizafop, quizalofop,quizalofop-P and trifop; phenylenediamine herbicides such as dinitramineand prodiamine; pyrazolyl herbicides such as benzofenap, pyrazolynate,pyrasulfotole, pyrazoxyfen, pyroxasulfone and topramezone;pyrazolyiplpiethyl herbicides such as fluazolate and pyraflufen;pyridaziiie herbicides such as credazine, pyridafol and pyridate;pyridazitiotte herbicides such as brompyrazon, chloridazon, dimidazon,flufenpyr, metflurazon, norflurazon, oxapyrazon and pydanon; pyridinieherbicides such as aminopyralid, cliodinate, clopyralid, dithiopyr,fluoroxypyr, haloxydine, picloram, picolinafen, pyriclor, thiazopyr andtriclopyr; pyrimidinediamitie herbicides such as iprymidam andtioclorim; quaternary ammonium herbicides such as cyperquat,diethamquat, difenzoquat, diquat, morfamquat and paraquat; thiocarbamateherbicides such as butylate, cycloate, di-allate, EPTC, esprocarb,ethiolate, isopolinate, methiobencarb, molinate, orbencarb, pebulate,prosulfocarb, pyributicarb, sulfallate, thiobencarb, tiocarbazil,tri-allate and vernolate; thiocarbonate herbicides such as dimexano, EXDand proxan; thiourea herbicides such as methiuron; triazine herbicidessuch as dipropetryn, triaziflam and trihydroxytriazine; chlorotriazineherbicides such as atrazine, chlorazine, cyanazine, cyprazine,eglinazine, ipazine, mesoprazine, procyazine, proglinazine, propazine,sebuthylazine, simazine, terbuthylazine and trietazine; methoxytriazineherbicides such as atraton, methometon, prometon, secbumeton, simetonand terbumeton; methylthiotriazine herbicides such as ametryn,aziprotryne, cyanatryn, desmetryn, dimethametryn, methoprotryne,prometryn, simetryn and terbutryn; triazinone herbicides such asametridione, amibuzin, hexazinone, isomethiozin, metamitron andmetribuzin; triazole herbicides such as amitrole, cafenstrole, epronazand flupoxam; triazolone herbicides such as amicarbazone, bencarbazone,carfentrazone, flucarbazone, propoxycarbazone, sulfentrazone andthiencarbazone-methyl; triazolopyrimidine herbicides such ascloransulam, diclosulam, florasulam, flumetsulam, metosulam, penoxsulamand pyroxsulam; uracil herbicides such as butafenacil, bromacil,flupropacil, isocil, lenacil and terbacil; 3-phenyluracils; ureaherbicides such as benzthiazuron, cumyluron, cycluron, dichloralurea,diflufenzopyr, isonoruron, isouron, methabenzthiazuron, monisouron andnoruron; phenylurea herbicides such as anisuron, buturon, chlorbromuron,chloreturon, chlorotoluron, chloroxuron, daimuron, difenoxuron,dimefuron, diuron, fenuron, fluometuron, fluothiuron, isoproturon,linuron, methiuron, methyldymron, metobenzuron, metobromuron, metoxuron,monolinuron, monuron, neburon, parafluoron, phenobenzuron, siduron,tetrafluoron and thidiazuron; pyrimidinylsulfonylurea herbicides such asamidosulfuron, azimsulfuron, bensulfuron, chlorimuron, cyclosulfamuron,ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron,foramsulfuron, halosulfuron, imazosulfuron, mesosulfuron, nicosulfuron,orthosulfamuron, oxasulfuron, primisulfuron, pyrazosulfuron,rimsulfuron, sulfometuron, sulfosulfuron and trifloxysulfuron;triazinylsulfonylurea herbicides such as chlorsulfuron, cinosulfuron,ethametsulfuron, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron,triasulfuron, tribenuron, triflusulfuron and tritosulfuron;thiadiazolylurea herbicides such as buthiuron, ethidimuron, tebuthiuron,thiazafluoron and thidiazuron; and unclassified herbicides such asacrolein, allyl alcohol, azafenidin, benazolin, bentazone,benzobicyclon, buthidazole, calcium cyanamide, cambendichlor,chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, cinmethylin,clomazone, CPMF, cresol, ortho-dichlorobenzene, dimepiperate, endothal,fluoromidine, fluridone, fluorochloridone, flurtamone, fluthiacet,indanofan, methazole, methyl isothiocyanate, nipyraclofen, OCH,oxadiargyl, oxadiazon, oxaziclomefone, pentachlorophenol, pentoxazone,phenylmercury acetate, pinoxaden, prosulfalin, pyribenzoxim, pyriftalid,quinoclamine, rhodethanil, sulglycapin, thidiazimin, tridiphane,trimeturon, tripropindan and tritac.

Before an insecticide can be used or sold commercially, such compositionundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, and international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by another on the product registrant's behalf. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user and/or seller withproduct registration approval. Thereafter, in that locality where theproduct registration is granted and supported, such user and/or sellermay use and/or sell such compound.

Any theory, mechanism of operation, proof, or finding stated herein ismeant to further enhance understanding of the present invention and isnot intended to make the present invention in any way dependent uponsuch theory, mechanism of operation, proof, or finding. It should beunderstood that while the use of the word preferable, preferably orpreferred in the description above indicates that the feature sodescribed may be more desirable, it nonetheless may not be necessary andembodiments lacking the same may be contemplated as within the scope ofthe invention, that scope being defined by the claims that follow. Inreading the claims it is intended that when words such as “a,” “an,” “atleast one,” “at least a portion” are used there is no intention to limitthe claim to only one item unless specifically stated to the contrary inthe claim. Further, when the language “at least a portion” and/or “aportion” is used the item may include a portion and/or the entire itemunless specifically stated to the contrary. While the invention has beenillustrated and described in detail in the drawings and foregoingdescription, the same is to be considered as illustrative and notrestrictive in character, it being understood that only the selectedembodiments have been shown and described and that all changes,modifications and equivalents that come within the spirit of theinvention as defined herein or by any of the following claims aredesired to be protected.

What is claimed is:
 1. A method, comprising: providing a compositionincluding a first ratio between stereoisomers of a compound having thefollowing formula (I):

wherein X represents NO₂, CN or COOR⁴; L represents a single bond or R¹,S and L taken together represents a 4-, 5- or 6-membered ring; R¹represents (C₁-C₄) alkyl; R² and R³ are distinct from each other andindividually represent hydrogen, methyl, ethyl, fluoro, chloro or bromo;n is 1 when L represents a single bond or is 0 when R¹, S and L takentogether represents a 4-, 5- or 6-membered ring; Y represents (C₁-C₄)haloalkyl, F, Cl, Br, or I; and R⁴ represents (C₁-C₃) alkyl; and heatingthe composition in a manner effective to provide a second, distinctratio between the stereoisomers.
 2. The method of claim 1, wherein Lrepresents a single bond and the compound includes the followingstructure:

wherein X represents NO₂, CN or COOR⁴; R¹ represents (C₁-C₄) alkyl; R²and R³ are distinct from each other and individually represent hydrogen,methyl, ethyl, fluoro, chloro or bromo; Y represents (C₁-C₄) haloalkyl,F, Cl, Br, or I; and R⁴ represents (C₁-C₃) alkyl.
 3. The method of claim1, wherein R¹, S and L taken together form a 5-membered ring and n is 0and the compound includes the following structure:

wherein X represents NO₂, CN or COOR⁴; Y represents (C₁-C₄) haloalkyl,F, Cl, Br, or I; and R⁴ represents (C₁-C₃) alkyl.
 4. The method of claim1, wherein X represents NO₂ or CN, Y represents —CF₃, and R² and R³independently represent hydrogen, methyl or ethyl.
 5. The method ofclaim 1, wherein the composition further includes a spinosyn selectedfrom the group consisting of spinetoram, spinosad and mixtures thereof.6. The method of claim 1, which further includes, subsequent to saidheating, applying to a locus where control is desired aninsect-inactivating amount of the composition.
 7. The method of claim 1,wherein the heating is performed at a minimum of about 50° C. from aboutfour to about seventy two hours.
 8. The method of claim 1, wherein thecomposition includes a first pair of stereoisomers and a second pair ofstereoisomers, and the first ratio is between the first and second pairsof stereoisomers and includes a value of about 1:2.
 9. The method ofclaim 8, wherein the second ratio is between the first and second pairsof stereoisomers and includes a value of at least 1:1.
 10. The method ofclaim 9, wherein the second ratio includes a value in the range of about3:1 to about 100:1.
 11. The method of claim 10, wherein the second ratioincludes a value in the range of about 3:1 to about 40:1.
 12. The methodof claim 9, wherein the second ratio includes a value greater than 10:1.